Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2018, 68, 394–424. [CrossRef]
Duma, N.; Santana-Davila, R.; Molina, J.R. Non-Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment. Mayo Clin. Proc. 2019, 94, 1623–1640. [CrossRef] [PubMed]
Reck, M.; Rabe, K.F. Precision Diagnosis and Treatment for Advanced Non-Small-Cell Lung Cancer. N. Engl. J. Med. 2017, 377, 849–861. [CrossRef] [PubMed]
Korpanty, G.J.; Graham, D.M.; Vincent, M.D.; Leighl, N.B. Biomarkers That Currently Affect Clinical Practice in Lung Cancer: EGFR, ALK, MET, ROS-1, and KRAS. Front. Oncol. 2014, 4, 204. [CrossRef]
Prelaj, A.; Tay, R.; Ferrara, R.; Chaput, N.; Besse, B.; Califano, R. Predictive Biomarkers of Response for Immune Checkpoint Inhibitors in Non-Small-Cell Lung Cancer. Eur. J. Cancer 2019, 106, 144–159. [CrossRef]
Allemani, C.; Matsuda, T.; Di Carlo, V.; Harewood, R.; Matz, M.; Nikšić, M.; Bonaventure, A.; Valkov, M.; Johnson, C.J.; Estève, J.; et al. Global Surveillance of Trends in Cancer Survival 2000-14 (CONCORD-3): Analysis of Individual Records for 37 513 025 Patients Diagnosed with One of 18 Cancers from 322 Population-Based Registries in 71 Countries. Lancet 2018, 391, 1023–1075. [CrossRef]
Chen, P.-S.; Chiu, W.-T.; Hsu, P.-L.; Lin, S.-C.; Peng, I.-C.; Wang, C.-Y.; Tsai, S.-J. Pathophysiological Implications of Hypoxia in Human Diseases. J. Biomed. Sci. 2020, 27, 63. [CrossRef]
Mouronte-Roibás, C.; Leiro-Fernández, V.; Fernández-Villar, A.; Botana-Rial, M.; Ramos-Hernández, C.; Ruano-Ravina, A. COPD, Emphysema and the Onset of Lung Cancer. A Systematic Review. Cancer Lett. 2016, 382, 240–244. [CrossRef]
Semenza, G.L. Hypoxia-Inducible Factors in Physiology and Medicine. Cell 2012, 148, 399–408. [CrossRef]
Fajersztajn, L.; Veras, M.M. Hypoxia: From Placental Development to Fetal Programming. Birth Defects Res. 2017, 109, 1377–1385. [CrossRef]
Kurihara, T. Roles of Hypoxia Response in Retinal Development and Pathophysiology. Keio J. Med. 2018, 67, 1–9. [CrossRef]
Vadivel, A.; Alphonse, R.S.; Etches, N.; van Haaften, T.; Collins, J.J.P.; O’Reilly, M.; Eaton, F.; Thébaud, B. Hypoxia-Inducible Factors Promote Alveolar Development and Regeneration. Am. J. Respir. Cell Mol. Biol. 2014, 50, 96–105. [CrossRef] [PubMed]
Woik, N.; Kroll, J. Regulation of Lung Development and Regeneration by the Vascular System. Cell. Mol. Life Sci. 2015, 72, 2709–2718. [CrossRef]
Ullmann, P.; Nurmik, M.; Begaj, R.; Haan, S.; Letellier, E. Hypoxia-and MicroRNA-Induced Metabolic Reprogramming of Tumor-Initiating Cells. Cells 2019, 8, 528. [CrossRef]
Huertas-Castaño, C.; Gómez-Muñoz, M.A.; Pardal, R.; Vega, F.M. Hypoxia in the Initiation and Progression of Neuroblastoma Tumours. Int. J. Mol. Sci. 2019, 21, 39. [CrossRef]
Pouysségur, J.; Dayan, F.; Mazure, N.M. Hypoxia Signalling in Cancer and Approaches to Enforce Tumour Regression. Nature 2006, 441, 437–443. [CrossRef]
Peng, G.; Liu, Y. Hypoxia-Inducible Factors in Cancer Stem Cells and Inflammation. Trends Pharmacol. Sci. 2015, 36, 374–383. [CrossRef]
Schito, L. Hypoxia-Dependent Angiogenesis and Lymphangiogenesis in Cancer. Adv. Exp. Med. Biol. 2019, 1136, 71–85. [CrossRef] [PubMed]
Vito, A.; El-Sayes, N.; Mossman, K. Hypoxia-Driven Immune Escape in the Tumor Microenvironment. Cells 2020, 9, 992. [CrossRef]
Luo, W.; Wang, Y. Hypoxia Mediates Tumor Malignancy and Therapy Resistance. Adv. Exp. Med. Biol. 2019, 1136, 1–18. [CrossRef]
Jackson, A.L.; Zhou, B.; Kim, W.Y. HIF, Hypoxia and the Role of Angiogenesis in Non-Small Cell Lung Cancer. Expert Opin. Ther. Targets 2010, 14, 1047–1057. [CrossRef]
Pugh, C.W.; Ratcliffe, P.J. New Horizons in Hypoxia Signaling Pathways. Exp. Cell Res. 2017, 356, 116–121. [CrossRef]
Zhao, Z.; Mu, H.; Li, Y.; Liu, Y.; Zou, J.; Zhu, Y. Clinicopathological and Prognostic Value of Hypoxia-Inducible Factor-1α in Breast Cancer: A Meta-Analysis Including 5177 Patients. Clin. Transl. Oncol. 2020. [CrossRef] [PubMed]
Dahia, P.L.M.; Toledo, R.A. Recognizing Hypoxia in Phaeochromocytomas and Paragangliomas. Nat. Rev. Endocrinol. 2020, 16, 191–192. [CrossRef]
Fuchs, Q.; Pierrevelcin, M.; Messe, M.; Lhermitte, B.; Blandin, A.-F.; Papin, C.; Coca, A.; Dontenwill, M.; Entz-Werlé, N. Hypoxia Inducible Factors’ Signaling in Pediatric High-Grade Gliomas: Role, Modelization and Innovative Targeted Approaches. Cancers 2020, 12, 979. [CrossRef]
Wielockx, B.; Grinenko, T.; Mirtschink, P.; Chavakis, T. Hypoxia Pathway Proteins in Normal and Malignant Hematopoiesis. Cells 2019, 8, 155. [CrossRef]
Bryant, J.L.; Meredith, S.L.; Williams, K.J.; White, A. Targeting Hypoxia in the Treatment of Small Cell Lung Cancer. Lung Cancer 2014, 86, 126–132. [CrossRef]
Nabavi, N.; Bennewith, K.L.; Churg, A.; Wang, Y.; Collins, C.C.; Mutti, L. Switching off Malignant Mesothelioma: Exploiting the Hypoxic Microenvironment. Genes Cancer 2016, 7, 340–354. [CrossRef] [PubMed]
Papkovsky, D.B.; Dmitriev, R.I. Imaging of Oxygen and Hypoxia in Cell and Tissue Samples. Cell. Mol. Life Sci. 2018, 75, 2963–2980. [CrossRef]
Semenza, G.L. HIF-1: Mediator of Physiological and Pathophysiological Responses to Hypoxia. J. Appl. Physiol. 2000, 88, 1474–1480. [CrossRef] [PubMed]
Shimoda, L.A.; Semenza, G.L. HIF and the Lung: Role of Hypoxia-Inducible Factors in Pulmonary Development and Disease. Am. J. Respir. Crit. Care Med. 2011, 183, 152–156. [CrossRef] [PubMed]
Lee, J.W.; Ko, J.; Ju, C.; Eltzschig, H.K. Hypoxia Signaling in Human Diseases and Therapeutic Targets. Exp. Mol. Med. 2019, 51, 1–13. [CrossRef] [PubMed]
Balamurugan, K. HIF-1 at the Crossroads of Hypoxia, Inflammation, and Cancer. Int. J. Cancer 2016, 138, 1058–1066. [CrossRef] [PubMed]
Tirpe, A.A.; Gulei, D.; Ciortea, S.M.; Crivii, C.; Berindan-Neagoe, I. Hypoxia: Overview on Hypoxia-Mediated Mechanisms with a Focus on the Role of HIF Genes. Int. J. Mol. Sci. 2019, 20, 6140. [CrossRef] [PubMed]
Goudar, R.K.; Vlahovic, G. Hypoxia, Angiogenesis, and Lung Cancer. Curr. Oncol. Rep. 2008, 10, 277–282. [CrossRef] [PubMed]
Yang, S.-L.; Ren, Q.-G.; Wen, L.; Hu, J.-L. Clinicopathological and Prognostic Significance of Hypoxia-Inducible Factor-1 Alpha in Lung Cancer: A Systematic Review with Meta-Analysis. J. Huazhong Univ. Sci. Technol. Med. Sci. 2016, 36, 321–327. [CrossRef]
Li, J.; Zhang, G.; Wang, X.; Li, X.-F. Is Carbonic Anhydrase IX a Validated Target for Molecular Imaging of Cancer and Hypoxia? Future Oncol. 2015, 11, 1531–1541. [CrossRef] [PubMed]
Albadari, N.; Deng, S.; Li, W. The Transcriptional Factors HIF-1 and HIF-2 and Their Novel Inhibitors in Cancer Therapy. Expert Opin. Drug Discov. 2019, 14, 667–682. [CrossRef]
Xiong, Q.; Liu, B.; Ding, M.; Zhou, J.; Yang, C.; Chen, Y. Hypoxia and Cancer Related Pathology. Cancer Lett. 2020, 486, 1–7. [CrossRef]
Laddha, A.P.; Kulkarni, Y.A. VEGF and FGF-2: Promising Targets for the Treatment of Respiratory Disorders. Respir. Med. 2019, 156, 33–46. [CrossRef] [PubMed]
Xu, C.; Wang, W.; Wang, Y.; Zhang, X.; Yan, J.; Yu, L. Serum Angiopoietin-2 as a Clinical Marker for Lung Cancer in Patients with Solitary Pulmonary Nodules. Ann. Clin. Lab. Sci. 2016, 46, 60–64. [PubMed]
Xu, Y.; Zhang, Y.; Wang, Z.; Chen, N.; Zhou, J.; Liu, L. The Role of Serum Angiopoietin-2 Levels in Progression and Prognosis of Lung Cancer: A Meta-Analysis. Medicine 2017, 96, e8063. [CrossRef] [PubMed]
Kizaka-Kondoh, S.; Konse-Nagasawa, H. Significance of Nitroimidazole Compounds and Hypoxia-Inducible Factor-1 for Imaging Tumor Hypoxia. Cancer Sci. 2009, 100, 1366–1373. [CrossRef] [PubMed]
Qin, S.; Yi, M.; Jiao, D.; Li, A.; Wu, K. Distinct Roles of VEGFA and ANGPT2 in Lung Adenocarcinoma and Squamous Cell Carcinoma. J. Cancer 2020, 11, 153–167. [CrossRef] [PubMed]
Ren, W.; Mi, D.; Yang, K.; Cao, N.; Tian, J.; Li, Z.; Ma, B. The Expression of Hypoxia-Inducible Factor-1α and Its Clinical Significance in Lung Cancer: A Systematic Review and Meta-Analysis. Swiss Med. Wkly. 2013, 143, w13855. [CrossRef]
Liu, J.; Liu, Y.; Gong, W.; Kong, X.; Wang, C.; Wang, S.; Liu, A. Prognostic Value of Insulin-like Growth Factor 2 MRNA-Binding Protein 3 and Vascular Endothelial Growth Factor-A in Patients with Primary Non-Small-Cell Lung Cancer. Oncol. Lett. 2019, 18, 4744–4752. [CrossRef] [PubMed]
Yuan, A.; Yu, C.J.; Chen, W.J.; Lin, F.Y.; Kuo, S.H.; Luh, K.T.; Yang, P.C. Correlation of Total VEGF MRNA and Protein Expression with Histologic Type, Tumor Angiogenesis, Patient Survival and Timing of Relapse in Non-Small-Cell Lung Cancer. Int. J. Cancer 2000, 89, 475–483. [CrossRef]
Gao, Z.-J.; Wang, Y.; Yuan, W.-D.; Yuan, J.-Q.; Yuan, K. HIF-2α Not HIF-1α Overexpression Confers Poor Prognosis in Non-Small Cell Lung Cancer. Tumour Biol. 2017, 39, 1010428317709637. [CrossRef] [PubMed]
Yeh, S.-J.; Chang, C.-A.; Li, C.-W.; Wang, L.H.-C.; Chen, B.-S. Comparing Progression Molecular Mechanisms between Lung Adenocarcinoma and Lung Squamous Cell Carcinoma Based on Genetic and Epigenetic Networks: Big Data Mining and Genome-Wide Systems Identification. Oncotarget 2019, 10, 3760–3806. [CrossRef] [PubMed]
Lee, S.; Kang, H.G.; Choi, J.E.; Lee, J.H.; Kang, H.J.; Baek, S.A.; Lee, E.; Seok, Y.; Lee, W.K.; Lee, S.Y.; et al. The Different Effect of VEGF Polymorphisms on the Prognosis of Non-Small Cell Lung Cancer According to Tumor Histology. J. Korean Med. Sci. 2016, 31, 1735–1741. [CrossRef]
Eilertsen, M.; Pettersen, I.; Andersen, S.; Martinez, I.; Donnem, T.; Busund, L.-T.; Bremnes, R.M. In NSCLC, VEGF-A Response to Hypoxia May Differ between Squamous Cell and Adenocarcinoma Histology. Anticancer Res. 2012, 32, 4729–4736.
Najafi, M.; Mortezaee, K.; Majidpoor, J. Cancer Stem Cell (CSC) Resistance Drivers. Life Sci. 2019, 234, 116781. [CrossRef] [PubMed]
Batlle, E.; Clevers, H. Cancer Stem Cells Revisited. Nat. Med. 2017, 23, 1124–1134. [CrossRef]
Tong, W.-W.; Tong, G.-H.; Liu, Y. Cancer Stem Cells and Hypoxia-Inducible Factors (Review). Int. J. Oncol. 2018, 53, 469–476. [CrossRef] [PubMed]
Bajaj, J.; Diaz, E.; Reya, T. Stem Cells in Cancer Initiation and Progression. J. Cell Biol. 2020, 219. [CrossRef] [PubMed]
Saforo, D.; Omer, L.; Smolenkov, A.; Barve, A.; Casson, L.; Boyd, N.; Clark, G.; Siskind, L.; Beverly, L. Primary Lung Cancer Samples Cultured under Microenvironment-Mimetic Conditions Enrich for Mesenchymal Stem-like Cells That Promote Metastasis. Sci. Rep. 2019, 9, 4177. [CrossRef] [PubMed]
Kang, N.; Choi, S.Y.; Kim, B.N.; Yeo, C.D.; Park, C.K.; Kim, Y.K.; Kim, T.-J.; Lee, S.-B.; Lee, S.H.; Park, J.Y.; et al. Hypoxia-Induced Cancer Stemness Acquisition Is Associated with CXCR4 Activation by Its Aberrant Promoter Demethylation. BMC Cancer 2019, 19, 148. [CrossRef] [PubMed]
Chen, J.; Xu, R.; Xia, J.; Huang, J.; Su, B.; Wang, S. Aspirin Inhibits Hypoxia-Mediated Lung Cancer Cell Stemness and Exosome Function. Pathol. Res. Pract. 2019, 215, 152379. [CrossRef] [PubMed]
Zhao, M.; Zhang, Y.; Zhang, H.; Wang, S.; Zhang, M.; Chen, X.; Wang, H.; Zeng, G.; Chen, X.; Liu, G.; et al. Hypoxia-Induced Cell Stemness Leads to Drug Resistance and Poor Prognosis in Lung Adenocarcinoma. Lung Cancer 2015, 87, 98–106. [CrossRef]
Tam, S.Y.; Wu, V.W.C.; Law, H.K.W. Hypoxia-Induced Epithelial-Mesenchymal Transition in Cancers: HIF-1α and Beyond. Front. Oncol. 2020, 10, 486. [CrossRef]
Yeo, C.D.; Kang, N.; Choi, S.Y.; Kim, B.N.; Park, C.K.; Kim, J.W.; Kim, Y.K.; Kim, S.J. The Role of Hypoxia on the Acquisition of Epithelial-Mesenchymal Transition and Cancer Stemness: A Possible Link to Epigenetic Regulation. Korean J. Intern. Med. 2017, 32, 589–599. [CrossRef] [PubMed]
Emprou, C.; Le Van Quyen, P.; Jégu, J.; Prim, N.; Weingertner, N.; Guérin, E.; Pencreach, E.; Legrain, M.; Voegeli, A.-C.; Leduc, C.; et al. SNAI2 and TWIST1 in Lymph Node Progression in Early Stages of NSCLC Patients. Cancer Med. 2018. [CrossRef]
Wei, L.; Sun, J.-J.; Cui, Y.-C.; Jiang, S.-L.; Wang, X.-W.; Lv, L.-Y.; Xie, L.; Song, X.-R. Twist May Be Associated with Invasion and Metastasis of Hypoxic NSCLC Cells. Tumour Biol. 2016, 37, 9979–9987. [CrossRef] [PubMed]
Zhang, J.; Wang, J.; Xing, H.; Li, Q.; Zhao, Q.; Li, J. Down-Regulation of FBP1 by ZEB1-Mediated Repression Confers to Growth and Invasion in Lung Cancer Cells. Mol. Cell. Biochem. 2016, 411, 331–340. [CrossRef]
Ruan, J.; Zhang, L.; Yan, L.; Liu, Y.; Yue, Z.; Chen, L.; Wang, A.-Y.; Chen, W.; Zheng, S.; Wang, S.; et al. Inhibition of Hypoxia-Induced Epithelial Mesenchymal Transition by Luteolin in Non-Small Cell Lung Cancer Cells. Mol. Med. Rep. 2012, 6, 232–238. [CrossRef]
Kong, X.; Zhao, Y.; Li, X.; Tao, Z.; Hou, M.; Ma, H. Overexpression of HIF-2α-Dependent NEAT1 Promotes the Progression of Non-Small Cell Lung Cancer through MiR-101-3p/SOX9/Wnt/β-Catenin Signal Pathway. Cell. Physiol. Biochem. 2019, 52, 368–381. [CrossRef]
Liu, X.; Chen, H.; Xu, X.; Ye, M.; Cao, H.; Xu, L.; Hou, Y.; Tang, J.; Zhou, D.; Bai, Y.; et al. Insulin-like Growth Factor-1 Receptor Knockdown Enhances Radiosensitivity via the HIF-1α Pathway and Attenuates ATM/H2AX/53BP1 DNA Repair Activation in Human Lung Squamous Carcinoma Cells. Oncol. Lett. 2018, 16, 1332–1340. [CrossRef]
Kim, I.-G.; Lee, J.-H.; Kim, S.-Y.; Hwang, H.-M.; Kim, T.-R.; Cho, E.-W. Hypoxia-Inducible Transgelin 2 Selects Epithelial-to-Mesenchymal Transition and γ-Radiation-Resistant Subtypes by Focal Adhesion Kinase-Associated Insulin-like Growth Factor 1 Receptor Activation in Non-Small-Cell Lung Cancer Cells. Cancer Sci. 2018, 109, 3519–3531. [CrossRef] [PubMed]
Nurwidya, F.; Takahashi, F.; Kobayashi, I.; Murakami, A.; Kato, M.; Minakata, K.; Nara, T.; Hashimoto, M.; Yagishita, S.; Baskoro, H.; et al. Treatment with Insulin-like Growth Factor 1 Receptor Inhibitor Reverses Hypoxia-Induced Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer. Biochem. Biophys. Res. Commun. 2014, 455, 332–338. [CrossRef]
Wang, J.; Tian, L.; Khan, M.N.; Zhang, L.; Chen, Q.; Zhao, Y.; Yan, Q.; Fu, L.; Liu, J. Ginsenoside Rg3 Sensitizes Hypoxic Lung Cancer Cells to Cisplatin via Blocking of NF-KB Mediated Epithelial-Mesenchymal Transition and Stemness. Cancer Lett. 2018, 415, 73–85. [CrossRef]
Wu, C.-E.; Zhuang, Y.-W.; Zhou, J.-Y.; Liu, S.-L.; Zou, X.; Wu, J.; Wang, R.-P.; Shu, P. Nm23-H1 Inhibits Hypoxia Induced Epithelial-Mesenchymal Transition and Stemness in Non-Small Cell Lung Cancer Cells. Biol. Chem. 2019, 400, 765–776. [CrossRef]
Tan, S.; Xia, L.; Yi, P.; Han, Y.; Tang, L.; Pan, Q.; Tian, Y.; Rao, S.; Oyang, L.; Liang, J.; et al. Exosomal MiRNAs in Tumor Microenvironment. J. Exp. Clin. Cancer Res. 2020, 39, 67. [CrossRef] [PubMed]
Farina, A.R.; Cappabianca, L.; Sebastiano, M.; Zelli, V.; Guadagni, S.; Mackay, A.R. Hypoxia-Induced Alternative Splicing: The 11th Hallmark of Cancer. J. Exp. Clin. Cancer Res. 2020, 39, 110. [CrossRef] [PubMed]
Zhang, X.; Sai, B.; Wang, F.; Wang, L.; Wang, Y.; Zheng, L.; Li, G.; Tang, J.; Xiang, J. Hypoxic BMSC-Derived Exosomal MiRNAs Promote Metastasis of Lung Cancer Cells via STAT3-Induced EMT. Mol. Cancer 2019, 18, 40. [CrossRef] [PubMed]
Ren, W.; Hou, J.; Yang, C.; Wang, H.; Wu, S.; Wu, Y.; Zhao, X.; Lu, C. Extracellular Vesicles Secreted by Hypoxia Pre-Challenged Mesenchymal Stem Cells Promote Non-Small Cell Lung Cancer Cell Growth and Mobility as Well as Macrophage M2 Polarization via MiR-21-5p Delivery. J. Exp. Clin. Cancer Res. 2019, 38, 62. [CrossRef]
Kao, S.-H.; Cheng, W.-C.; Wang, Y.-T.; Wu, H.-T.; Yeh, H.-Y.; Chen, Y.-J.; Tsai, M.-H.; Wu, K.-J. Regulation of MiRNA Biogenesis and Histone Modification by K63-Polyubiquitinated DDX17 Controls Cancer Stem-like Features. Cancer Res. 2019, 79, 2549–2563. [CrossRef]
Chen, X.; Wu, L.; Li, D.; Xu, Y.; Zhang, L.; Niu, K.; Kong, R.; Gu, J.; Xu, Z.; Chen, Z.; et al. Radiosensitizing Effects of MiR-18a-5p on Lung Cancer Stem-like Cells via Downregulating Both ATM and HIF-1α. Cancer Med. 2018, 7, 3834–3847. [CrossRef] [PubMed]
Kumar, A.; Deep, G. Exosomes in Hypoxia-Induced Remodeling of the Tumor Microenvironment. Cancer Lett. 2020, 488, 1–8. [CrossRef]
Jafari, R.; Rahbarghazi, R.; Ahmadi, M.; Hassanpour, M.; Rezaie, J. Hypoxic Exosomes Orchestrate Tumorigenesis: Molecular Mechanisms and Therapeutic Implications. J. Transl. Med. 2020, 18, 474. [CrossRef]
Noman, M.Z.; Messai, Y.; Muret, J.; Hasmim, M.; Chouaib, S. Crosstalk between CTC, Immune System and Hypoxic Tumor Microenvironment. Cancer Microenviron. 2014, 7, 153–160. [CrossRef]
Wang, B.; Zhao, Q.; Zhang, Y.; Liu, Z.; Zheng, Z.; Liu, S.; Meng, L.; Xin, Y.; Jiang, X. Targeting Hypoxia in the Tumor Microenvironment: A Potential Strategy to Improve Cancer Immunotherapy. J. Exp. Clin. Cancer Res. 2021, 40, 24. [CrossRef]
Hajizadeh, F.; Okoye, I.; Esmaily, M.; Ghasemi Chaleshtari, M.; Masjedi, A.; Azizi, G.; Irandoust, M.; Ghalamfarsa, G.; Jadidi-Niaragh, F. Hypoxia Inducible Factors in the Tumor Microenvironment as Therapeutic Targets of Cancer Stem Cells. Life Sci. 2019, 237, 116952. [CrossRef] [PubMed]
Giannone, G.; Ghisoni, E.; Genta, S.; Scotto, G.; Tuninetti, V.; Turinetto, M.; Valabrega, G. Immuno-Metabolism and Microenviron-ment in Cancer: Key Players for Immunotherapy. Int. J. Mol. Sci. 2020, 21, 4414. [CrossRef]
Mittal, V.; El Rayes, T.; Narula, N.; McGraw, T.E.; Altorki, N.K.; Barcellos-Hoff, M.H. The Microenvironment of Lung Cancer and Therapeutic Implications. Adv. Exp. Med. Biol. 2016, 890, 75–110. [CrossRef]
D’Ignazio, L.; Batie, M.; Rocha, S. Hypoxia and Inflammation in Cancer, Focus on HIF and NF-KB. Biomedicines 2017, 5, 21. [CrossRef]
Cassetta, L.; Kitamura, T. Macrophage Targeting: Opening New Possibilities for Cancer Immunotherapy. Immunology 2018, 155, 285–293. [CrossRef]
Bremnes, R.M.; Busund, L.-T.; Kilvær, T.L.; Andersen, S.; Richardsen, E.; Paulsen, E.E.; Hald, S.; Khanehkenari, M.R.; Cooper, W.A.; Kao, S.C.; et al. The Role of Tumor-Infiltrating Lymphocytes in Development, Progression, and Prognosis of Non-Small Cell Lung Cancer. J. Thorac. Oncol. 2016, 11, 789–800. [CrossRef]
Henze, A.-T.; Mazzone, M. The Impact of Hypoxia on Tumor-Associated Macrophages. J. Clin. Investig. 2016, 126, 3672–3679. [CrossRef] [PubMed]
Poh, A.R.; Ernst, M. Targeting Macrophages in Cancer: From Bench to Bedside. Front. Oncol. 2018, 8, 49. [CrossRef]
Jeong, H.; Kim, S.; Hong, B.-J.; Lee, C.-J.; Kim, Y.-E.; Bok, S.; Oh, J.-M.; Gwak, S.-H.; Yoo, M.Y.; Lee, M.S.; et al. Tumor-Associated Macrophages Enhance Tumor Hypoxia and Aerobic Glycolysis. Cancer Res. 2019, 79, 795–806. [CrossRef] [PubMed]
Silva, V.L.; Al-Jamal, W.T. Exploiting the Cancer Niche: Tumor-Associated Macrophages and Hypoxia as Promising Synergistic Targets for Nano-Based Therapy. J. Control. Release 2017, 253, 82–96. [CrossRef] [PubMed]
Noël, G.; Langouo Fontsa, M.; Willard-Gallo, K. The Impact of Tumor Cell Metabolism on T Cell-Mediated Immune Responses and Immuno-Metabolic Biomarkers in Cancer. Semin. Cancer Biol. 2018, 52, 66–74. [CrossRef] [PubMed]
Chang, W.H.; Forde, D.; Lai, A.G. A Novel Signature Derived from Immunoregulatory and Hypoxia Genes Predicts Prognosis in Liver and Five Other Cancers. J. Transl. Med. 2019, 17, 14. [CrossRef] [PubMed]
Giatromanolaki, A.; Harris, A.L.; Banham, A.H.; Contrafouris, C.A.; Koukourakis, M.I. Carbonic Anhydrase 9 (CA9) Expression in Non-Small-Cell Lung Cancer: Correlation with Regulatory FOXP3+T-Cell Tumour Stroma Infiltration. Br. J. Cancer 2020, 122, 1205–1210. [CrossRef]
Akbarpour, M.; Khalyfa, A.; Qiao, Z.; Gileles-Hillel, A.; Almendros, I.; Farré, R.; Gozal, D. Altered CD8+ T-Cell Lymphocyte Function and TC1 Cell Stemness Contribute to Enhanced Malignant Tumor Properties in Murine Models of Sleep Apnea. Sleep 2017, 40. [CrossRef] [PubMed]
Noman, M.Z.; Buart, S.; Romero, P.; Ketari, S.; Janji, B.; Mari, B.; Mami-Chouaib, F.; Chouaib, S. Hypoxia-Inducible MiR-210 Regulates the Susceptibility of Tumor Cells to Lysis by Cytotoxic T Cells. Cancer Res. 2012, 72, 4629–4641. [CrossRef] [PubMed]
Noman, M.Z.; Janji, B.; Kaminska, B.; Van Moer, K.; Pierson, S.; Przanowski, P.; Buart, S.; Berchem, G.; Romero, P.; Mami-Chouaib, F.; et al. Blocking Hypoxia-Induced Autophagy in Tumors Restores Cytotoxic T-Cell Activity and Promotes Regression. Cancer Res. 2011, 71, 5976–5986. [CrossRef]
Giatromanolaki, A.; Koukourakis, I.M.; Balaska, K.; Mitrakas, A.G.; Harris, A.L.; Koukourakis, M.I. Programmed Death-1 Receptor (PD-1) and PD-Ligand-1 (PD-L1) Expression in Non-Small Cell Lung Cancer and the Immune-Suppressive Effect of Anaerobic Glycolysis. Med. Oncol. 2019, 36, 76. [CrossRef]
Koh, Y.W.; Lee, S.J.; Han, J.-H.; Haam, S.; Jung, J.; Lee, H.W. PD-L1 Protein Expression in Non-Small-Cell Lung Cancer and Its Relationship with the Hypoxia-Related Signaling Pathways: A Study Based on Immunohistochemistry and RNA Sequencing Data. Lung Cancer 2019, 129, 41–47. [CrossRef]
Corrales, L.; Scilla, K.; Caglevic, C.; Miller, K.; Oliveira, J.; Rolfo, C. Immunotherapy in Lung Cancer: A New Age in Cancer Treatment. Adv. Exp. Med. Biol. 2018, 995, 65–95. [CrossRef] [PubMed]
Sharpe, A.H.; Pauken, K.E. The Diverse Functions of the PD1 Inhibitory Pathway. Nat. Rev. Immunol. 2018, 18, 153–167. [CrossRef] [PubMed]
Gatenby, R.A.; Gillies, R.J. Why Do Cancers Have High Aerobic Glycolysis? Nat. Rev. Cancer 2004, 4, 891–899. [CrossRef] [PubMed]
Koukourakis, M.I.; Giatromanolaki, A.; Bougioukas, G.; Sivridis, E. Lung Cancer: A Comparative Study of Metabolism Related Protein Expression in Cancer Cells and Tumor Associated Stroma. Cancer Biol. Ther. 2007, 6, 1476–1479. [CrossRef] [PubMed]
Chang, W.H.; Lai, A.G. Transcriptional Landscape of DNA Repair Genes Underpins a Pan-Cancer Prognostic Signature Associated with Cell Cycle Dysregulation and Tumor Hypoxia. DNA Repair 2019, 78, 142–153. [CrossRef]
Wang, Z.; Wei, Y.; Zhang, R.; Su, L.; Gogarten, S.M.; Liu, G.; Brennan, P.; Field, J.K.; McKay, J.D.; Lissowska, J.; et al. Multi-Omics Analysis Reveals a HIF Network and Hub Gene EPAS1 Associated with Lung Adenocarcinoma. EBioMedicine 2018, 32, 93–101. [CrossRef]
Buffa, F.M.; Harris, A.L.; West, C.M.; Miller, C.J. Large Meta-Analysis of Multiple Cancers Reveals a Common, Compact and Highly Prognostic Hypoxia Metagene. Br. J. Cancer 2010, 102, 428–435. [CrossRef]
Chen, Y.-L.; Zhang, Y.; Wang, J.; Chen, N.; Fang, W.; Zhong, J.; Liu, Y.; Qin, R.; Yu, X.; Sun, Z.; et al. A 17 Gene Panel for Non-Small-Cell Lung Cancer Prognosis Identified through Integrative Epigenomic-Transcriptomic Analyses of Hypoxia-Induced Epithelial-Mesenchymal Transition. Mol. Oncol. 2019, 13, 1490–1502. [CrossRef]
Ferrara, M.G.; Di Noia, V.; D’Argento, E.; Vita, E.; Damiano, P.; Cannella, A.; Ribelli, M.; Pilotto, S.; Milella, M.; Tortora, G.; et al. Oncogene-Addicted Non-Small-Cell Lung Cancer: Treatment Opportunities and Future Perspectives. Cancers 2020, 12, 1196. [CrossRef] [PubMed]
Bhandari, V.; Hoey, C.; Liu, L.Y.; Lalonde, E.; Ray, J.; Livingstone, J.; Lesurf, R.; Shiah, Y.-J.; Vujcic, T.; Huang, X.; et al. Molecular Landmarks of Tumor Hypoxia across Cancer Types. Nat. Genet. 2019, 51, 308–318. [CrossRef]
Hu, X.; Fang, Y.; Zheng, J.; He, Y.; Zan, X.; Lin, S.; Li, X.; Li, H.; You, C. The Association between HIF-1α Polymorphism and Cancer Risk: A Systematic Review and Meta-Analysis. Tumour Biol. 2014, 35, 903–916. [CrossRef]
Li, Y.; Li, C.; Shi, H.; Lou, L.; Liu, P. The Association between the Rs11549465 Polymorphism in the Hif-1α Gene and Cancer Risk: A Meta-Analysis. Int. J. Clin. Exp. Med. 2015, 8, 1561–1574.
Jain, L.; Vargo, C.A.; Danesi, R.; Sissung, T.M.; Price, D.K.; Venzon, D.; Venitz, J.; Figg, W.D. The Role of Vascular Endothelial Growth Factor SNPs as Predictive and Prognostic Markers for Major Solid Tumors. Mol. Cancer Ther. 2009, 8, 2496–2508. [CrossRef]
Heist, R.S.; Zhai, R.; Liu, G.; Zhou, W.; Lin, X.; Su, L.; Asomaning, K.; Lynch, T.J.; Wain, J.C.; Christiani, D.C. VEGF Polymorphisms and Survival in Early-Stage Non-Small-Cell Lung Cancer. J. Clin. Oncol. 2008, 26, 856–862. [CrossRef]
Wouters, A.; Boeckx, C.; Vermorken, J.B.; Van den Weyngaert, D.; Peeters, M.; Lardon, F. The Intriguing Interplay between Therapies Targeting the Epidermal Growth Factor Receptor, the Hypoxic Microenvironment and Hypoxia-Inducible Factors. Curr. Pharm. Des. 2013, 19, 907–917. [CrossRef]
Qi, H.; Wang, S.; Wu, J.; Yang, S.; Gray, S.; Ng, C.S.H.; Du, J.; Underwood, M.J.; Li, M.-Y.; Chen, G.G. EGFR-AS1/HIF2A Regulates the Expression of FOXP3 to Impact the Cancer Stemness of Smoking-Related Non-Small Cell Lung Cancer. Ther. Adv. Med. Oncol. 2019, 11. [CrossRef] [PubMed]
Wang, T.; Niki, T.; Goto, A.; Ota, S.; Morikawa, T.; Nakamura, Y.; Ohara, E.; Ishikawa, S.; Aburatani, H.; Nakajima, J.; et al. Hypoxia Increases the Motility of Lung Adenocarcinoma Cell Line A549 via Activation of the Epidermal Growth Factor Receptor Pathway. Cancer Sci. 2007, 98, 506–511. [CrossRef]
Swinson, D.E.B.; O’Byrne, K.J. Interactions between Hypoxia and Epidermal Growth Factor Receptor in Non-Small-Cell Lung Cancer. Clin. Lung Cancer 2006, 7, 250–256. [CrossRef]
Swinson, D.E.B.; Jones, J.L.; Cox, G.; Richardson, D.; Harris, A.L.; O’Byrne, K.J. Hypoxia-Inducible Factor-1 Alpha in Non Small Cell Lung Cancer: Relation to Growth Factor, Protease and Apoptosis Pathways. Int. J. Cancer 2004, 111, 43–50. [CrossRef]
Yuan, X.-H.; Yang, J.; Wang, X.-Y.; Zhang, X.-L.; Qin, T.-T.; Li, K. Association between EGFR/KRAS Mutation and Expression of VEGFA, VEGFR and VEGFR2 in Lung Adenocarcinoma. Oncol. Lett. 2018, 16, 2105–2112. [CrossRef]
Meng, S.; Wang, G.; Lu, Y.; Fan, Z. Functional Cooperation between HIF-1α and c-Jun in Mediating Primary and Acquired Resistance to Gefitinib in NSCLC Cells with Activating Mutation of EGFR. Lung Cancer 2018, 121, 82–90. [CrossRef]
Lu, Y.; Liu, Y.; Oeck, S.; Zhang, G.J.; Schramm, A.; Glazer, P.M. Hypoxia Induces Resistance to EGFR Inhibitors in Lung Cancer Cells via Upregulation of FGFR1 and the MAPK Pathway. Cancer Res. 2020. [CrossRef]
Reiterer, M.; Colaço, R.; Emrouznejad, P.; Jensen, A.; Rundqvist, H.; Johnson, R.S.; Branco, C. Acute and Chronic Hypoxia Differentially Predispose Lungs for Metastases. Sci. Rep. 2019, 9, 10246. [CrossRef]
Bader, S.B.; Dewhirst, M.W.; Hammond, E.M. Cyclic Hypoxia: An Update on Its Characteristics, Methods to Measure It and Biological Implications in Cancer. Cancers 2020, 13, 23. [CrossRef]
Moldogazieva, N.T.; Mokhosoev, I.M.; Terentiev, A.A. Metabolic Heterogeneity of Cancer Cells: An Interplay between HIF-1, GLUTs, and AMPK. Cancers 2020, 12, 862. [CrossRef] [PubMed]
Thunnissen, E.; Kerr, K.M.; Herth, F.J.F.; Lantuejoul, S.; Papotti, M.; Rintoul, R.C.; Rossi, G.; Skov, B.G.; Weynand, B.; Bubendorf, L.; et al. The Challenge of NSCLC Diagnosis and Predictive Analysis on Small Samples. Practical Approach of a Working Group. Lung Cancer 2012, 76, 1–18. [CrossRef]
Zheng, H.; Ning, Y.; Zhan, Y.; Liu, S.; Yang, Y.; Wen, Q.; Fan, S. Co-Expression of PD-L1 and HIF-1α Predicts Poor Prognosis in Patients with Non-Small Cell Lung Cancer after Surgery. J. Cancer 2021, 12, 2065–2072. [CrossRef]
Afsar, C.U.; Uysal, P. HIF-1α Levels in Patients Receiving Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Carcinoma. Rev. Assoc. Med. Bras. 2019, 65, 1295–1299. [CrossRef] [PubMed]
Ostheimer, C.; Bache, M.; Güttler, A.; Kotzsch, M.; Vordermark, D. A Pilot Study on Potential Plasma Hypoxia Markers in the Radiotherapy of Non-Small Cell Lung Cancer. Osteopontin, Carbonic Anhydrase IX and Vascular Endothelial Growth Factor. Strahlenther. Onkol. 2014, 190, 276–282. [CrossRef]
Mandeville, H.C.; Ng, Q.S.; Daley, F.M.; Barber, P.R.; Pierce, G.; Finch, J.; Burke, M.; Bell, A.; Townsend, E.R.; Kozarski, R.; et al. Operable Non-Small Cell Lung Cancer: Correlation of Volumetric Helical Dynamic Contrast-Enhanced CT Parameters with Immunohistochemical Markers of Tumor Hypoxia. Radiology 2012, 264, 581–589. [CrossRef]
Surov, A.; Meyer, H.J.; Wienke, A. Standardized Uptake Values Derived from 18F-FDG PET May Predict Lung Cancer Microvessel Density and Expression of KI 67, VEGF, and HIF-1α but Not Expression of Cyclin D1, PCNA, EGFR, PD L1, and P53. Contrast Media Mol. Imaging 2018, 2018, 9257929. [CrossRef]
Carvalho, S.; Troost, E.G.C.; Bons, J.; Menheere, P.; Lambin, P.; Oberije, C. Prognostic Value of Blood-Biomarkers Related to Hypoxia, Inflammation, Immune Response and Tumour Load in Non-Small Cell Lung Cancer-A Survival Model with External Validation. Radiother. Oncol. 2016, 119, 487–494. [CrossRef]
Ostheimer, C.; Gunther, S.; Bache, M.; Vordermark, D.; Multhoff, G. Dynamics of Heat Shock Protein 70 Serum Levels as a Predictor of Clinical Response in Non-Small-Cell Lung Cancer and Correlation with the Hypoxia-Related Marker Osteopontin. Front. Immunol. 2017, 8, 1305. [CrossRef]
Ostheimer, C.; Evers, C.; Bache, M.; Reese, T.; Vordermark, D. Prognostic Implications of the Co-Detection of the Urokinase Plasminogen Activator System and Osteopontin in Patients with Non-Small-Cell Lung Cancer Undergoing Radiotherapy and Correlation with Gross Tumor Volume. Strahlenther. Onkol. 2018, 194, 539–551. [CrossRef]
Suwinski, R.; Giglok, M.; Galwas-Kliber, K.; Idasiak, A.; Jochymek, B.; Deja, R.; Maslyk, B.; Mrochem-Kwarciak, J.; Butkiewicz, D. Blood Serum Proteins as Biomarkers for Prediction of Survival, Locoregional Control and Distant Metastasis Rate in Radiotherapy and Radio-Chemotherapy for Non-Small Cell Lung Cancer. BMC Cancer 2019, 19, 427. [CrossRef]
Delmotte, P.; Martin, B.; Paesmans, M.; Berghmans, T.; Mascaux, C.; Meert, A.P.; Steels, E.; Verdebout, J.M.; Lafitte, J.J.; Sculier, J.P. VEGF and survival of patients with lung cancer: A systematic literature review and meta-analysis. Rev. Mal. Respir. 2002, 19, 577–584.
Shibaki, R.; Murakami, S.; Shinno, Y.; Matsumoto, Y.; Yoshida, T.; Goto, Y.; Kanda, S.; Horinouchi, H.; Fujiwara, Y.; Yamamoto, N.; et al. Predictive Value of Serum VEGF Levels for Elderly Patients or for Patients with Poor Performance Status Receiving Anti-PD-1 Antibody Therapy for Advanced Non-Small-Cell Lung Cancer. Cancer Immunol. Immunother. 2020, 69, 1229–1236. [CrossRef]
Bremnes, R.M.; Camps, C.; Sirera, R. Angiogenesis in Non-Small Cell Lung Cancer: The Prognostic Impact of Neoangiogenesis and the Cytokines VEGF and BFGF in Tumours and Blood. Lung Cancer 2006, 51, 143–158. [CrossRef] [PubMed]
Papadaki, C.; Monastirioti, A.; Rounis, K.; Makrakis, D.; Kalbakis, K.; Nikolaou, C.; Mavroudis, D.; Agelaki, S. Circulating MicroRNAs Regulating DNA Damage Response and Responsiveness to Cisplatin in the Prognosis of Patients with Non-Small Cell Lung Cancer Treated with First-Line Platinum Chemotherapy. Cancers 2020, 12, 1282. [CrossRef]
O’Connor, J.P.B.; Robinson, S.P.; Waterton, J.C. Imaging Tumour Hypoxia with Oxygen-Enhanced MRI and BOLD MRI. Br. J. Radiol. 2019, 92, 20180642. [CrossRef] [PubMed]
Salem, A.; Little, R.A.; Latif, A.; Featherstone, A.K.; Babur, M.; Peset, I.; Cheung, S.; Watson, Y.; Tessyman, V.; Mistry, H.; et al. Oxygen-Enhanced MRI Is Feasible, Repeatable, and Detects Radiotherapy-Induced Change in Hypoxia in Xenograft Models and in Patients with Non-Small Cell Lung Cancer. Clin. Cancer Res. 2019, 25, 3818–3829. [CrossRef]
Challapalli, A.; Carroll, L.; Aboagye, E.O. Molecular Mechanisms of Hypoxia in Cancer. Clin. Transl. Imaging 2017, 5, 225–253. [CrossRef]
Thawani, R.; McLane, M.; Beig, N.; Ghose, S.; Prasanna, P.; Velcheti, V.; Madabhushi, A. Radiomics and Radiogenomics in Lung Cancer: A Review for the Clinician. Lung Cancer 2018, 115, 34–41. [CrossRef]
Seijo, L.M.; Peled, N.; Ajona, D.; Boeri, M.; Field, J.K.; Sozzi, G.; Pio, R.; Zulueta, J.J.; Spira, A.; Massion, P.P.; et al. Biomarkers in Lung Cancer Screening: Achievements, Promises, and Challenges. J. Thorac. Oncol. 2019, 14, 343–357. [CrossRef]
Even, A.J.G.; Reymen, B.; La Fontaine, M.D.; Das, M.; Jochems, A.; Mottaghy, F.M.; Belderbos, J.S.A.; De Ruysscher, D.; Lambin, P.; van Elmpt, W. Predicting Tumor Hypoxia in Non-Small Cell Lung Cancer by Combining CT, FDG PET and Dynamic Contrast-Enhanced CT. Acta Oncol. 2017, 56, 1591–1596. [CrossRef]
Marcu, L.G.; Forster, J.C.; Bezak, E. The Potential Role of Radiomics and Radiogenomics in Patient Stratification by Tumor Hypoxia Status. J. Am. Coll. Radiol. 2019, 16, 1329–1337. [CrossRef] [PubMed]
Xu, Z.; Li, X.-F.; Zou, H.; Sun, X.; Shen, B. 18F-Fluoromisonidazole in Tumor Hypoxia Imaging. Oncotarget 2017, 8, 94969–94979. [CrossRef]
Nehmeh, S.A.; Schwartz, J.; Grkovski, M.; Yeung, I.; Laymon, C.M.; Muzi, M.; Humm, J.L. Inter-Operator Variability in Compartmental Kinetic Analysis of 18F-Fluoromisonidazole Dynamic PET. Clin. Imaging 2018, 49, 121–127. [CrossRef] [PubMed]
Schwartz, J.; Grkovski, M.; Rimner, A.; Schöder, H.; Zanzonico, P.B.; Carlin, S.D.; Staton, K.D.; Humm, J.L.; Nehmeh, S.A. Pharmacokinetic Analysis of Dynamic 18F-Fluoromisonidazole PET Data in Non-Small Cell Lung Cancer. J. Nucl. Med. 2017, 58, 911–919. [CrossRef]
Thureau, S.; Chaumet-Riffaud, P.; Modzelewski, R.; Fernandez, P.; Tessonnier, L.; Vervueren, L.; Cachin, F.; Berriolo-Riedinger, A.; Olivier, P.; Kolesnikov-Gauthier, H.; et al. Interobserver Agreement of Qualitative Analysis and Tumor Delineation of 18F-Fluoromisonidazole and 3’-Deoxy-3’-18F-Fluorothymidine PET Images in Lung Cancer. J. Nucl. Med. 2013, 54, 1543–1550. [CrossRef] [PubMed]
Texte, E.; Gouel, P.; Thureau, S.; Lequesne, J.; Barres, B.; Edet-Sanson, A.; Decazes, P.; Vera, P.; Hapdey, S. Impact of the Bayesian Penalized Likelihood Algorithm (Q.Clear® ) in Comparison with the OSEM Reconstruction on Low Contrast PET Hypoxic Images. EJNMMI Phys. 2020, 7, 28. [CrossRef]
Zschaeck, S.; Steinbach, J.; Troost, E.G.C. FMISO as a Biomarker for Clinical Radiation Oncology. Recent Results Cancer Res. 2016, 198, 189–201. [CrossRef] [PubMed]
Zegers, C.M.L.; van Elmpt, W.; Szardenings, K.; Kolb, H.; Waxman, A.; Subramaniam, R.M.; Moon, D.H.; Brunetti, J.C.; Srinivas, S.M.; Lambin, P.; et al. Repeatability of Hypoxia PET Imaging Using [18 F]HX4 in Lung and Head and Neck Cancer Patients: A Prospective Multicenter Trial. Eur. J. Nucl. Med. Mol. Imaging 2015, 42, 1840–1849. [CrossRef]
Zegers, C.M.L.; van Elmpt, W.; Reymen, B.; Even, A.J.G.; Troost, E.G.C.; Ollers, M.C.; Hoebers, F.J.P.; Houben, R.M.A.; Eriksson, J.; Windhorst, A.D.; et al. In Vivo Quantification of Hypoxic and Metabolic Status of NSCLC Tumors Using [18 F]HX4 and [18 F]FDG-PET/CT Imaging. Clin. Cancer Res. 2014, 20, 6389–6397. [CrossRef] [PubMed]
Zegers, C.M.L.; van Elmpt, W.; Wierts, R.; Reymen, B.; Sharifi, H.; Öllers, M.C.; Hoebers, F.; Troost, E.G.C.; Wanders, R.; van Baardwijk, A.; et al. Hypoxia Imaging with [18 F]HX4 PET in NSCLC Patients: Defining Optimal Imaging Parameters. Radiother. Oncol. 2013, 109, 58–64. [CrossRef]
Wack, L.J.; Mönnich, D.; van Elmpt, W.; Zegers, C.M.L.; Troost, E.G.C.; Zips, D.; Thorwarth, D. Comparison of [18 F]-FMISO, [18 F]-FAZA and [18 F]-HX4 for PET Imaging of Hypoxia–a Simulation Study. Acta Oncol. 2015, 54, 1370–1377. [CrossRef]
Peeters, S.G.J.A.; Zegers, C.M.L.; Lieuwes, N.G.; van Elmpt, W.; Eriksson, J.; van Dongen, G.A.M.S.; Dubois, L.; Lambin, P. A Comparative Study of the Hypoxia PET Tracers [18 F]HX4, [18 F]FAZA, and [18 F]FMISO in a Preclinical Tumor Model. Int. J. Radiat. Oncol. Biol. Phys. 2015, 91, 351–359. [CrossRef]
Huang, T.; Civelek, A.C.; Li, J.; Jiang, H.; Ng, C.K.; Postel, G.C.; Shen, B.; Li, X.-F. Tumor Microenvironment-Dependent 18F-FDG, 18F-Fluorothymidine, and 18F-Misonidazole Uptake: A Pilot Study in Mouse Models of Human Non-Small Cell Lung Cancer. J. Nucl. Med. 2012, 53, 1262–1268. [CrossRef] [PubMed]
Yu, B.; Zhu, X.; Liang, Z.; Sun, Y.; Zhao, W.; Chen, K. Clinical Usefulness of 18F-FDG PET/CT for the Detection of Distant Metastases in Patients with Non-Small Cell Lung Cancer at Initial Staging: A Meta-Analysis. Cancer Manag. Res. 2018, 10, 1859–1864. [CrossRef]
Heiden, B.T.; Chen, G.; Hermann, M.; Brown, R.K.J.; Orringer, M.B.; Lin, J.; Chang, A.C.; Carrott, P.W.; Lynch, W.R.; Zhao, L.; et al. 18F-FDG PET Intensity Correlates with a Hypoxic Gene Signature and Other Oncogenic Abnormalities in Operable Non-Small Cell Lung Cancer. PLoS ONE 2018, 13, e0199970. [CrossRef]
Thureau, S.; Modzelewski, R.; Bohn, P.; Hapdey, S.; Gouel, P.; Dubray, B.; Vera, P. Comparison of Hypermetabolic and Hypoxic Volumes Delineated on [18 F]FDG and [18 F]Fluoromisonidazole PET/CT in Non-Small-Cell Lung Cancer Patients. Mol. Imaging Biol. 2019. [CrossRef] [PubMed]
Sanduleanu, S.; van der Wiel, A.M.A.; Lieverse, R.I.Y.; Marcus, D.; Ibrahim, A.; Primakov, S.; Wu, G.; Theys, J.; Yaromina, A.; Dubois, L.J.; et al. Hypoxia PET Imaging with [18 F]-HX4-A Promising Next-Generation Tracer. Cancers 2020, 12, 1322. [CrossRef]
Vera, P.; Bohn, P.; Edet-Sanson, A.; Salles, A.; Hapdey, S.; Gardin, I.; Ménard, J.-F.; Modzelewski, R.; Thiberville, L.; Dubray, B. Simultaneous Positron Emission Tomography (PET) Assessment of Metabolism with18 F-Fluoro-2-Deoxy-d-Glucose (FDG), Proliferation with18 F-Fluoro-Thymidine (FLT), and Hypoxia with18 fluoro-Misonidazole (F-Miso) before and during Radiotherapy in Patients with Non-Small-Cell Lung Cancer (NSCLC): A Pilot Study. Radiother. Oncol. 2011, 98, 109–116. [CrossRef]
Manafi-Farid, R.; Karamzade-Ziarati, N.; Vali, R.; Mottaghy, F.M.; Beheshti, M. 2-[18 F]FDG PET/CT Radiomics in Lung Cancer: An Overview of the Technical Aspect and Its Emerging Role in Management of the Disease. Methods 2020. [CrossRef]
van Elmpt, W.; Zegers, C.M.L.; Reymen, B.; Even, A.J.G.; Dingemans, A.-M.C.; Oellers, M.; Wildberger, J.E.; Mottaghy, F.M.; Das, M.; Troost, E.G.C.; et al. Multiparametric Imaging of Patient and Tumour Heterogeneity in Non-Small-Cell Lung Cancer: Quantification of Tumour Hypoxia, Metabolism and Perfusion. Eur. J. Nucl. Med. Mol. Imaging 2016, 43, 240–248. [CrossRef] [PubMed]
Ostheimer, C.; Schweyer, F.; Reese, T.; Bache, M.; Vordermark, D. The Relationship between Tumor Volume Changes and Serial Plasma Osteopontin Detection during Radical Radiotherapy of Non-Small-Cell Lung Cancer. Oncol. Lett. 2016, 12, 3449–3456. [CrossRef]
Rolfo, C.; Mack, P.C.; Scagliotti, G.V.; Baas, P.; Barlesi, F.; Bivona, T.G.; Herbst, R.S.; Mok, T.S.; Peled, N.; Pirker, R.; et al. Liquid Biopsy for Advanced Non-Small Cell Lung Cancer (NSCLC): A Statement Paper from the IASLC. J. Thorac. Oncol. 2018, 13, 1248–1268. [CrossRef] [PubMed]
Cortese, R.; Almendros, I.; Wang, Y.; Gozal, D. Tumor Circulating DNA Profiling in Xenografted Mice Exposed to Intermittent Hypoxia. Oncotarget 2015, 6, 556–569. [CrossRef] [PubMed]
Kulshreshtha, R.; Ferracin, M.; Wojcik, S.E.; Garzon, R.; Alder, H.; Agosto-Perez, F.J.; Davuluri, R.; Liu, C.-G.; Croce, C.M.; Negrini, M.; et al. A MicroRNA Signature of Hypoxia. Mol. Cell. Biol. 2007, 27, 1859–1867. [CrossRef] [PubMed]
Goodall, G.J.; Wickramasinghe, V.O. RNA in Cancer. Nat. Rev. Cancer 2021, 21, 22–36. [CrossRef]
Tartarone, A.; Rossi, E.; Lerose, R.; Mambella, G.; Calderone, G.; Zamarchi, R.; Aieta, M. Possible Applications of Circulating Tumor Cells in Patients with Non Small Cell Lung Cancer. Lung Cancer 2017, 107, 59–64. [CrossRef]
Kallergi, G.; Markomanolaki, H.; Giannoukaraki, V.; Papadaki, M.A.; Strati, A.; Lianidou, E.S.; Georgoulias, V.; Mavroudis, D.; Agelaki, S. Hypoxia-Inducible Factor-1alpha and Vascular Endothelial Growth Factor Expression in Circulating Tumor Cells of Breast Cancer Patients. Breast Cancer Res. 2009, 11, R84. [CrossRef] [PubMed]
Manjunath, Y.; Upparahalli, S.V.; Avella, D.M.; Deroche, C.B.; Kimchi, E.T.; Staveley-O’Carroll, K.F.; Smith, C.J.; Li, G.; Kaifi, J.T. PD-L1 Expression with Epithelial Mesenchymal Transition of Circulating Tumor Cells Is Associated with Poor Survival in Curatively Resected Non-Small Cell Lung Cancer. Cancers 2019, 11, 806. [CrossRef] [PubMed]
Francart, M.-E.; Lambert, J.; Vanwynsberghe, A.M.; Thompson, E.W.; Bourcy, M.; Polette, M.; Gilles, C. Epithelial-Mesenchymal Plasticity and Circulating Tumor Cells: Travel Companions to Metastases. Dev. Dyn. 2018, 247, 432–450. [CrossRef]
Chen, X.; Gole, J.; Gore, A.; He, Q.; Lu, M.; Min, J.; Yuan, Z.; Yang, X.; Jiang, Y.; Zhang, T.; et al. Non-Invasive Early Detection of Cancer Four Years before Conventional Diagnosis Using a Blood Test. Nat. Commun. 2020, 11, 3475. [CrossRef]
Chang, S.; Yim, S.; Park, H. The Cancer Driver Genes IDH1/2, JARID1C/KDM5C, and UTX/KDM6A: Crosstalk between Histone Demethylation and Hypoxic Reprogramming in Cancer Metabolism. Exp. Mol. Med. 2019, 51, 1–17. [CrossRef] [PubMed]
Zhang, K.; Wang, J.; Yang, L.; Yuan, Y.-C.; Tong, T.R.; Wu, J.; Yun, X.; Bonner, M.; Pangeni, R.; Liu, Z.; et al. Targeting Histone Methyltransferase G9a Inhibits Growth and Wnt Signaling Pathway by Epigenetically Regulating HP1α and APC2 Gene Expression in Non-Small Cell Lung Cancer. Mol. Cancer 2018, 17, 153. [CrossRef]
Xu, X.-H.; Bao, Y.; Wang, X.; Yan, F.; Guo, S.; Ma, Y.; Xu, D.; Jin, L.; Xu, J.; Wang, J. Hypoxic-Stabilized EPAS1 Proteins Transactivate DNMT1 and Cause Promoter Hypermethylation and Transcription Inhibition of EPAS1 in Non-Small Cell Lung Cancer. FASEB J. 2018, fj201700715. [CrossRef] [PubMed]
Li, T.; Mao, C.; Wang, X.; Shi, Y.; Tao, Y. Epigenetic Crosstalk between Hypoxia and Tumor Driven by HIF Regulation. J. Exp. Clin. Cancer Res. 2020, 39, 224. [CrossRef]
Cheng, X.; Yang, Y.; Fan, Z.; Yu, L.; Bai, H.; Zhou, B.; Wu, X.; Xu, H.; Fang, M.; Shen, A.; et al. MKL1 Potentiates Lung Cancer Cell Migration and Invasion by Epigenetically Activating MMP9 Transcription. Oncogene 2015, 34, 5570–5581. [CrossRef] [PubMed]
Oleksiewicz, U.; Liloglou, T.; Tasopoulou, K.-M.; Daskoulidou, N.; Gosney, J.R.; Field, J.K.; Xinarianos, G. COL1A1, PRPF40A, and UCP2 Correlate with Hypoxia Markers in Non-Small Cell Lung Cancer. J. Cancer Res. Clin. Oncol. 2017, 143, 1133–1141. [CrossRef] [PubMed]
Xu, X.-L.; Gong, Y.; Zhao, D.-P. Elevated PHD2 Expression Might Serve as a Valuable Biomarker of Poor Prognosis in Lung Adenocarcinoma, but No Lung Squamous Cell Carcinoma. Eur. Rev. Med. Pharmacol. Sci. 2018, 22, 8731–8739. [CrossRef] [PubMed]
Li, H.; Tong, L.; Tao, H.; Liu, Z. Genome-Wide Analysis of the Hypoxia-Related DNA Methylation-Driven Genes in Lung Adenocarcinoma Progression. Biosci. Rep. 2020, 40. [CrossRef] [PubMed]
Zhang, R.; Lai, L.; He, J.; Chen, C.; You, D.; Duan, W.; Dong, X.; Zhu, Y.; Lin, L.; Shen, S.; et al. EGLN2 DNA Methylation and Expression Interact with HIF1A to Affect Survival of Early-Stage NSCLC. Epigenetics 2019, 14, 118–129. [CrossRef] [PubMed]
Brahimi-Horn, M.C.; Giuliano, S.; Saland, E.; Lacas-Gervais, S.; Sheiko, T.; Pelletier, J.; Bourget, I.; Bost, F.; Féral, C.; Boulter, E.; et al. Knockout of Vdac1 Activates Hypoxia-Inducible Factor through Reactive Oxygen Species Generation and Induces Tumor Growth by Promoting Metabolic Reprogramming and Inflammation. Cancer Metab. 2015, 3, 8. [CrossRef]
Putra, A.C.; Tanimoto, K.; Arifin, M.; Hiyama, K. Hypoxia-Inducible Factor-1α Polymorphisms Are Associated with Genetic Aberrations in Lung Cancer. Respirology 2011, 16, 796–802. [CrossRef] [PubMed]
Xiao, P.; Chen, J.; Zhou, F.; Lu, C.; Yang, Q.; Tao, G.; Tao, Y.; Chen, J. Methylation of P16 in Exhaled Breath Condensate for Diagnosis of Non-Small Cell Lung Cancer. Lung Cancer 2014, 83, 56–60. [CrossRef] [PubMed]
Campanella, A.; De Summa, S.; Tommasi, S. Exhaled Breath Condensate Biomarkers for Lung Cancer. J. Breath Res. 2019, 13, 044002. [CrossRef]
Hompland, T.; Fjeldbo, C.S.; Lyng, H. Tumor Hypoxia as a Barrier in Cancer Therapy: Why Levels Matter. Cancers 2021, 13, 499. [CrossRef] [PubMed]
Wu, J.-Y.; Huang, T.-W.; Hsieh, Y.-T.; Wang, Y.-F.; Yen, C.-C.; Lee, G.-L.; Yeh, C.-C.; Peng, Y.-J.; Kuo, Y.-Y.; Wen, H.-T.; et al. Cancer-Derived Succinate Promotes Macrophage Polarization and Cancer Metastasis via Succinate Receptor. Mol. Cell 2020, 77, 213–227.e5. [CrossRef]
Dang, N.-H.T.; Singla, A.K.; Mackay, E.M.; Jirik, F.R.; Weljie, A.M. Targeted Cancer Therapeutics: Biosynthetic and Energetic Pathways Characterized by Metabolomics and the Interplay with Key Cancer Regulatory Factors. Curr. Pharm. Des. 2014, 20, 2637–2647. [CrossRef] [PubMed]
Pernemalm, M.; De Petris, L.; Branca, R.M.; Forshed, J.; Kanter, L.; Soria, J.-C.; Girard, P.; Validire, P.; Pawitan, Y.; van den Oord, J.; et al. Quantitative Proteomics Profiling of Primary Lung Adenocarcinoma Tumors Reveals Functional Perturbations in Tumor Metabolism. J. Proteome Res. 2013, 12, 3934–3943. [CrossRef]
Ping, W.; Jiang, W.-Y.; Chen, W.-S.; Sun, W.; Fu, X.-N. Expression and Significance of Hypoxia Inducible Factor-1α and Lysyl Oxidase in Non-Small Cell Lung Cancer. Asian Pac. J. Cancer Prev. 2013, 14, 3613–3618. [CrossRef] [PubMed]
Carrillo de Santa Pau, E.; Arias, F.C.; Caso Peláez, E.; Muñoz Molina, G.M.; Sánchez Hernández, I.; Muguruza Trueba, I.; Moreno Balsalobre, R.; Sacristán López, S.; Gómez Pinillos, A.; del Val Toledo Lobo, M. Prognostic Significance of the Expression of Vascular Endothelial Growth Factors A, B, C, and D and Their Receptors R1, R2, and R3 in Patients with Nonsmall Cell Lung Cancer. Cancer 2009, 115, 1701–1712. [CrossRef] [PubMed]
Feng, Y.; Wang, W.; Hu, J.; Ma, J.; Zhang, Y.; Zhang, J. Expression of VEGF-C and VEGF-D as Significant Markers for Assessment of Lymphangiogenesis and Lymph Node Metastasis in Non-Small Cell Lung Cancer. Anat. Rec. 2010, 293, 802–812. [CrossRef] [PubMed]
Saintigny, P.; Kambouchner, M.; Ly, M.; Gomes, N.; Sainte-Catherine, O.; Vassy, R.; Czernichow, S.; Letoumelin, P.; Breau, J.-L.; Bernaudin, J.-F.; et al. Vascular Endothelial Growth Factor-C and Its Receptor VEGFR-3 in Non-Small-Cell Lung Cancer: Concurrent Expression in Cancer Cells from Primary Tumour and Metastatic Lymph Node. Lung Cancer 2007, 58, 205–213. [CrossRef]
Maekawa, S.; Iwasaki, A.; Shirakusa, T.; Enatsu, S.; Kawakami, T.; Kuroki, M.; Kuroki, M. Correlation between Lymph Node Metastasis and the Expression of VEGF-C, VEGF-D and VEGFR-3 in T1 Lung Adenocarcinoma. Anticancer Res. 2007, 27, 3735–3741. [PubMed]
Takizawa, H.; Kondo, K.; Fujino, H.; Kenzaki, K.; Miyoshi, T.; Sakiyama, S.; Tangoku, A. The Balance of VEGF-C and VEGFR-3 MRNA Is a Predictor of Lymph Node Metastasis in Non-Small Cell Lung Cancer. Br. J. Cancer 2006, 95, 75–79. [CrossRef] [PubMed]
Lee, S.J.; Lee, S.Y.; Jeon, H.-S.; Park, S.H.; Jang, J.S.; Lee, G.Y.; Son, J.W.; Kim, C.H.; Lee, W.K.; Kam, S.; et al. Vascular Endothelial Growth Factor Gene Polymorphisms and Risk of Primary Lung Cancer. Cancer Epidemiol. Biomark. Prev. 2005, 14, 571–575. [CrossRef] [PubMed]
Liu, C.; Zhou, X.; Gao, F.; Qi, Z.; Zhang, Z.; Guo, Y. Correlation of Genetic Polymorphism of Vascular Endothelial Growth Factor Gene with Susceptibility to Lung Cancer. Cancer Gene Ther. 2015, 22, 312–316. [CrossRef] [PubMed]
Zhai, R.; Liu, G.; Zhou, W.; Su, L.; Heist, R.S.; Lynch, T.J.; Wain, J.C.; Asomaning, K.; Lin, X.; Christiani, D.C. Vascular Endothelial Growth Factor Genotypes, Haplotypes, Gender, and the Risk of Non-Small Cell Lung Cancer. Clin. Cancer Res. 2008, 14, 612–617. [CrossRef] [PubMed]
Yang, F.; Qin, Z.; Shao, C.; Liu, W.; Ma, L.; Shu, Y.; Shen, H. Association between VEGF Gene Polymorphisms and the Susceptibility to Lung Cancer: An Updated Meta-Analysis. Biomed. Res. Int. 2018, 2018, 9271215. [CrossRef]
Zhao, H.-L.; Yu, J.-H.; Huang, L.-S.; Li, P.-Z.; Lao, M.; Zhu, B.; Ou, C. Relationship between Vascular Endothelial Growth Factor-2578C > a Gene Polymorphism and Lung Cancer Risk: A Meta-Analysis. BMC Med. Genet. 2020, 21, 17. [CrossRef]
Li, H.-N.; He, T.; Zha, Y.-J.; Du, F.; Liu, J.; Lin, H.-R.; Yang, W.-Z. HIF-1α Rs11549465 C>T Polymorphism Contributes to Increased Cancer Susceptibility: Evidence from 49 Studies. J. Cancer 2019, 10, 5955–5963. [CrossRef] [PubMed]
Yan, Q.; Chen, P.; Wang, S.; Liu, N.; Zhao, P.; Gu, A. Association between HIF-1α C1772T/G1790A Polymorphisms and Cancer Susceptibility: An Updated Systematic Review and Meta-Analysis Based on 40 Case-Control Studies. BMC Cancer 2014, 14, 950. [CrossRef]
Xu, S.; Ying, K. Association between HIF-1α Gene Polymorphisms and Lung Cancer: A Meta-Analysis. Medicine 2020, 99, e20610. [CrossRef] [PubMed]
Burdett, S.; Pignon, J.P.; Tierney, J.; Tribodet, H.; Stewart, L.; Le Pechoux, C.; Aupérin, A.; Le Chevalier, T.; Stephens, R.J.; Arriagada, R.; et al. Adjuvant Chemotherapy for Resected Early-Stage Non-Small Cell Lung Cancer. Cochrane Database Syst. Rev. 2015, CD011430. [CrossRef]
Hui, E.P.; Chan, A.T.C.; Pezzella, F.; Turley, H.; To, K.-F.; Poon, T.C.W.; Zee, B.; Mo, F.; Teo, P.M.L.; Huang, D.P.; et al. Coex-pression of Hypoxia-Inducible Factors 1alpha and 2alpha, Carbonic Anhydrase IX, and Vascular Endothelial Growth Factor in Nasopharyngeal Carcinoma and Relationship to Survival. Clin. Cancer Res. 2002, 8, 2595–2604.
Yohena, T.; Yoshino, I.; Takenaka, T.; Kameyama, T.; Ohba, T.; Kuniyoshi, Y.; Maehara, Y. Upregulation of Hypoxia-Inducible Factor-1alpha MRNA and Its Clinical Significance in Non-Small Cell Lung Cancer. J. Thorac. Oncol. 2009, 4, 284–290. [CrossRef] [PubMed]
Honguero Martínez, A.F.; Arnau Obrer, A.; Figueroa Almazán, S.; Martínez Hernández, N.; Guijarro Jorge, R. Prognostic value of the expression of vascular endothelial growth factor A and hypoxia-inducible factor 1alpha in patients undergoing surgery for non-small cell lung cancer. Med. Clin. 2014, 142, 432–437. [CrossRef] [PubMed]
Kim, S.J.; Rabbani, Z.N.; Dewhirst, M.W.; Vujaskovic, Z.; Vollmer, R.T.; Schreiber, E.-G.; Oosterwijk, E.; Kelley, M.J. Expression of HIF-1alpha, CA IX, VEGF, and MMP-9 in Surgically Resected Non-Small Cell Lung Cancer. Lung Cancer 2005, 49, 325–335. [CrossRef] [PubMed]
Zheng, C.-L.; Qiu, C.; Shen, M.-X.; Qu, X.; Zhang, T.-H.; Zhang, J.-H.; Du, J.-J. Prognostic Impact of Elevation of Vascular Endothelial Growth Factor Family Expression in Patients with Non-Small Cell Lung Cancer: An Updated Meta-Analysis. Asian Pac. J. Cancer Prev. 2015, 16, 1881–1895. [CrossRef]
Liu, C.; Zhou, X.; Zhang, Z.; Guo, Y. Correlation of Gene Polymorphisms of Vascular Endothelial Growth Factor with Grade and Prognosis of Lung Cancer. BMC Med. Genet. 2020, 21, 86. [CrossRef] [PubMed]
Moreno Roig, E.; Yaromina, A.; Houben, R.; Groot, A.J.; Dubois, L.; Vooijs, M. Prognostic Role of Hypoxia-Inducible Factor-2α Tumor Cell Expression in Cancer Patients: A Meta-Analysis. Front. Oncol. 2018, 8, 224. [CrossRef] [PubMed]
Kinoshita, T.; Fujii, H.; Hayashi, Y.; Kamiyama, I.; Ohtsuka, T.; Asamura, H. Prognostic Significance of Hypoxic PET Using (18)F-FAZA and (62)Cu-ATSM in Non-Small-Cell Lung Cancer. Lung Cancer 2016, 91, 56–66. [CrossRef]
Even, A.J.G.; Reymen, B.; La Fontaine, M.D.; Das, M.; Mottaghy, F.M.; Belderbos, J.S.A.; De Ruysscher, D.; Lambin, P.; van Elmpt, W. Clustering of Multi-Parametric Functional Imaging to Identify High-Risk Subvolumes in Non-Small Cell Lung Cancer. Radiother. Oncol. 2017, 125, 379–384. [CrossRef]
Nardone, V.; Tini, P.; Pastina, P.; Botta, C.; Reginelli, A.; Carbone, S.F.; Giannicola, R.; Calabrese, G.; Tebala, C.; Guida, C.; et al. Radiomics Predicts Survival of Patients with Advanced Non-Small Cell Lung Cancer Undergoing PD-1 Blockade Using Nivolumab. Oncol. Lett. 2020, 19, 1559–1566. [CrossRef] [PubMed]
Baldini, E.; Tibaldi, C.; Delli Paoli, C. Chemo-Radiotherapy Integration in Unresectable Locally Advanced Non-Small-Cell Lung Cancer: A Review. Clin. Transl. Oncol. 2020. [CrossRef] [PubMed]
Grass, G.D.; Naghavi, A.O.; Abuodeh, Y.A.; Perez, B.A.; Dilling, T.J. Analysis of Relapse Events After Definitive Chemoradiother-apy in Locally Advanced Non-Small-Cell Lung Cancer Patients. Clin. Lung Cancer 2019, 20, e1–e7. [CrossRef] [PubMed]
Li, L.; Wei, Y.; Huang, Y.; Yu, Q.; Liu, W.; Zhao, S.; Zheng, J.; Lu, H.; Yu, J.; Yuan, S. To Explore a Representative Hypoxic Parameter to Predict the Treatment Response and Prognosis Obtained by [18 F]FMISO-PET in Patients with Non-Small Cell Lung Cancer. Mol. Imaging Biol. 2018, 20, 1061–1067. [CrossRef] [PubMed]
Trinkaus, M.E.; Blum, R.; Rischin, D.; Callahan, J.; Bressel, M.; Segard, T.; Roselt, P.; Eu, P.; Binns, D.; MacManus, M.P.; et al. Imaging of Hypoxia with 18F-FAZA PET in Patients with Locally Advanced Non-Small Cell Lung Cancer Treated with Definitive Chemoradiotherapy. J. Med. Imaging Radiat. Oncol. 2013, 57, 475–481. [CrossRef] [PubMed]
Guan, X.; Yin, M.; Wei, Q.; Zhao, H.; Liu, Z.; Wang, L.-E.; Yuan, X.; O’Reilly, M.S.; Komaki, R.; Liao, Z. Genotypes and Haplotypes of the VEGF Gene and Survival in Locally Advanced Non-Small Cell Lung Cancer Patients Treated with Chemoradiotherapy. BMC Cancer 2010, 10, 431. [CrossRef] [PubMed]
Bollineni, V.R.; Koole, M.J.B.; Pruim, J.; Brouwer, C.L.; Wiegman, E.M.; Groen, H.J.M.; Vlasman, R.; Halmos, G.B.; Oosting, S.F.; Langendijk, J.A.; et al. Dynamics of Tumor Hypoxia Assessed by 18F-FAZA PET/CT in Head and Neck and Lung Cancer Patients during Chemoradiation: Possible Implications for Radiotherapy Treatment Planning Strategies. Radiother. Oncol. 2014, 113, 198–203. [CrossRef]
Lavigne, J.; Suissa, A.; Verger, N.; Dos Santos, M.; Benadjaoud, M.; Mille-Hamard, L.; Momken, I.; Soysouvanh, F.; Buard, V.; Guipaud, O.; et al. Lung Stereotactic Arc Therapy in Mice: Development of Radiation Pneumopathy and Influence of HIF-1α Endothelial Deletion. Int. J. Radiat. Oncol. Biol. Phys. 2019, 104, 279–290. [CrossRef] [PubMed]
Minami-Shimmyo, Y.; Ohe, Y.; Yamamoto, S.; Sumi, M.; Nokihara, H.; Horinouchi, H.; Yamamoto, N.; Sekine, I.; Kubota, K.; Tamura, T. Risk Factors for Treatment-Related Death Associated with Chemotherapy and Thoracic Radiotherapy for Lung Cancer. J. Thorac. Oncol. 2012, 7, 177–182. [CrossRef]
Nieder, C.; Bremnes, R.M. Effects of Smoking Cessation on Hypoxia and Its Potential Impact on Radiation Treatment Effects in Lung Cancer Patients. Strahlenther. Onkol. 2008, 184, 605–609. [CrossRef]
Yin, M.; Liao, Z.; Yuan, X.; Guan, X.; O’Reilly, M.S.; Welsh, J.; Wang, L.-E.; Wei, Q. Polymorphisms of the Vascular Endothelial Growth Factor Gene and Severe Radiation Pneumonitis in Non-Small Cell Lung Cancer Patients Treated with Definitive Radiotherapy. Cancer Sci. 2012, 103, 945–950. [CrossRef]
Rankin, E.B.; Giaccia, A.J. Hypoxic Control of Metastasis. Science 2016, 352, 175–180. [CrossRef] [PubMed]
Najafi, M.; Farhood, B.; Mortezaee, K.; Kharazinejad, E.; Majidpoor, J.; Ahadi, R. Hypoxia in Solid Tumors: A Key Promoter of Cancer Stem Cell (CSC) Resistance. J. Cancer Res. Clin. Oncol. 2020, 146, 19–31. [CrossRef] [PubMed]
Schöning, J.P.; Monteiro, M.; Gu, W. Drug Resistance and Cancer Stem Cells: The Shared but Distinct Roles of Hypoxia-Inducible Factors HIF1α and HIF2α. Clin. Exp. Pharmacol. Physiol. 2017, 44, 153–161. [CrossRef]
Rohwer, N.; Cramer, T. Hypoxia-Mediated Drug Resistance: Novel Insights on the Functional Interaction of HIFs and Cell Death Pathways. Drug Resist. Updat. 2011, 14, 191–201. [CrossRef]
Xia, Y.; Jiang, L.; Zhong, T. The Role of HIF-1α in Chemo-/Radioresistant Tumors. Onco Targets Ther. 2018, 11, 3003–3011. [CrossRef] [PubMed]
Zhao, J.; Du, F.; Luo, Y.; Shen, G.; Zheng, F.; Xu, B. The Emerging Role of Hypoxia-Inducible Factor-2 Involved in Chemo/Radioresistance in Solid Tumors. Cancer Treat. Rev. 2015, 41, 623–633. [CrossRef] [PubMed]
Rankin, E.B.; Nam, J.-M.; Giaccia, A.J. Hypoxia: Signaling the Metastatic Cascade. Trends Cancer 2016, 2, 295–304. [CrossRef] [PubMed]
Johnson, R.W.; Sowder, M.E.; Giaccia, A.J. Hypoxia and Bone Metastatic Disease. Curr. Osteoporos. Rep. 2017, 15, 231–238. [CrossRef] [PubMed]
Pezzuto, A.; Perrone, G.; Orlando, N.; Citarella, F.; Ciccozzi, M.; Scarlata, S.; Tonini, G. A Close Relationship between HIF-1α Expression and Bone Metastases in Advanced NSCLC, a Retrospective Analysis. Oncotarget 2019, 10, 7071–7079. [CrossRef] [PubMed]
Pacheco, J.M.; Camidge, D.R.; Doebele, R.C.; Schenk, E. A Changing of the Guard: Immune Checkpoint Inhibitors With and Without Chemotherapy as First Line Treatment for Metastatic Non-Small Cell Lung Cancer. Front. Oncol. 2019, 9, 195. [CrossRef] [PubMed]
Paz-Ares, L.; Luft, A.; Vicente, D.; Tafreshi, A.; Gümüş, M.; Mazières, J.; Hermes, B.; Şenler, F.Ç.; Csőszi, T.; Fülöp, A.; et al. Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N. Engl. J. Med. 2018, 379, 2040–2051. [CrossRef] [PubMed]
Gandhi, L.; Rodríguez-Abreu, D.; Gadgeel, S.; Esteban, E.; Felip, E.; De Angelis, F.; Domine, M.; Clingan, P.; Hochmair, M.J.; Powell, S.F.; et al. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N. Engl. J. Med. 2018, 378, 2078–2092. [CrossRef] [PubMed]
Manoochehri Khoshinani, H.; Afshar, S.; Najafi, R. Hypoxia: A Double-Edged Sword in Cancer Therapy. Cancer Investig. 2016, 34, 536–545. [CrossRef]
Wu, F.; Zhang, J.; Liu, Y.; Zheng, Y.; Hu, N. HIF1α Genetic Variants and Protein Expressions Determine the Response to Platinum Based Chemotherapy and Clinical Outcome in Patients with Advanced NSCLC. Cell. Physiol. Biochem. 2013, 32, 1566–1576. [CrossRef]
Shingyoji, M.; Ando, S.; Nishimura, H.; Nakajima, T.; Ishikawa, A.; Itakura, M.; Iizasa, T.; Kimura, H. VEGF in Patients with Non-Small Cell Lung Cancer during Combination Chemotherapy of Carboplatin and Paclitaxel. Anticancer Res. 2009, 29, 2635–2639. [PubMed]
Naumnik, W.; Izycki, T.; Swidzińska, E.; Ossolińiska, M.; Chyczewska, E. Serum Levels of VEGF-C, VEGF-D, and SVEGF-R2 in Patients with Lung Cancer during Chemotherapy. Oncol. Res. 2007, 16, 445–451. [CrossRef] [PubMed]
Zeng, L.; Kizaka-Kondoh, S.; Itasaka, S.; Xie, X.; Inoue, M.; Tanimoto, K.; Shibuya, K.; Hiraoka, M. Hypoxia Inducible Factor-1 Influences Sensitivity to Paclitaxel of Human Lung Cancer Cell Lines under Normoxic Conditions. Cancer Sci. 2007, 98, 1394–1401. [CrossRef] [PubMed]
Sowa, T.; Menju, T.; Chen-Yoshikawa, T.F.; Takahashi, K.; Nishikawa, S.; Nakanishi, T.; Shikuma, K.; Motoyama, H.; Hijiya, K.; Aoyama, A.; et al. Hypoxia-Inducible Factor 1 Promotes Chemoresistance of Lung Cancer by Inducing Carbonic Anhydrase IX Expression. Cancer Med. 2017, 6, 288–297. [CrossRef]
Guo, Q.; Lan, F.; Yan, X.; Xiao, Z.; Wu, Y.; Zhang, Q. Hypoxia Exposure Induced Cisplatin Resistance Partially via Activating P53 and Hypoxia Inducible Factor-1α in Non-Small Cell Lung Cancer A549 Cells. Oncol. Lett. 2018, 16, 801–808. [CrossRef] [PubMed]
Deben, C.; Deschoolmeester, V.; De Waele, J.; Jacobs, J.; Van den Bossche, J.; Wouters, A.; Peeters, M.; Rolfo, C.; Smits, E.; Lardon, F.; et al. Hypoxia-Induced Cisplatin Resistance in Non-Small Cell Lung Cancer Cells Is Mediated by HIF-1α and Mutant P53 and Can Be Overcome by Induction of Oxidative Stress. Cancers 2018, 10, 126. [CrossRef]
Zhang, F.; Duan, S.; Tsai, Y.; Keng, P.C.; Chen, Y.; Lee, S.O.; Chen, Y. Cisplatin Treatment Increases Stemness through Upregulation of Hypoxia-Inducible Factors by Interleukin-6 in Non-Small Cell Lung Cancer. Cancer Sci. 2016, 107, 746–754. [CrossRef] [PubMed]
Shi, Y.; Fan, S.; Wu, M.; Zuo, Z.; Li, X.; Jiang, L.; Shen, Q.; Xu, P.; Zeng, L.; Zhou, Y.; et al. YTHDF1 Links Hypoxia Adaptation and Non-Small Cell Lung Cancer Progression. Nat. Commun. 2019, 10, 4892. [CrossRef] [PubMed]
Lu, Y.; Yu, L.-Q.; Zhu, L.; Zhao, N.; Zhou, X.-J.; Lu, X. Expression of HIF-1α and P-Gp in Non-Small Cell Lung Cancer and the Relationship with HPV Infection. Oncol. Lett. 2016, 12, 1455–1459. [CrossRef] [PubMed]
Shen, X.; Zhi, Q.; Wang, Y.; Li, Z.; Zhou, J.; Huang, J. Hypoxia Induces Multidrug Resistance via Enhancement of Epidermal Growth Factor-Like Domain 7 Expression in Non-Small Lung Cancer Cells. Chemotherapy 2017, 62, 172–180. [CrossRef] [PubMed]
Liu, S.; Qin, T.; Jia, Y.; Li, K. PD-L1 Expression Is Associated with VEGFA and LADC Patients’ Survival. Front. Oncol. 2019, 9, 189. [CrossRef]
Cubillos-Zapata, C.; Almendros, I.; Díaz-García, E.; Toledano, V.; Casitas, R.; Galera, R.; López-Collazo, E.; Farre, R.; Gozal, D.; García-Rio, F. Differential Effect of Intermittent Hypoxia and Sleep Fragmentation on PD-1/PD-L1 Upregulation. Sleep 2020, 43. [CrossRef]
Huang, M.-H.; Zhang, X.-B.; Wang, H.-L.; Li, L.-X.; Zeng, Y.-M.; Wang, M.; Zeng, H.-Q. Intermittent Hypoxia Enhances the Tumor Programmed Death Ligand 1 Expression in a Mouse Model of Sleep Apnea. Ann. Transl. Med. 2019, 7, 97. [CrossRef] [PubMed]
Cubillos-Zapata, C.; Balbás-García, C.; Avendaño-Ortiz, J.; Toledano, V.; Torres, M.; Almendros, I.; Casitas, R.; Zamarrón, E.; García-Sánchez, A.; Feliu, J.; et al. Age-Dependent Hypoxia-Induced PD-L1 Upregulation in Patients with Obstructive Sleep Apnoea. Respirology 2019, 24, 684–692. [CrossRef] [PubMed]
Chang, W.H.; Lai, A.G. Aberrations in Notch-Hedgehog Signalling Reveal Cancer Stem Cells Harbouring Conserved Oncogenic Properties Associated with Hypoxia and Immunoevasion. Br. J. Cancer 2019, 121, 666–678. [CrossRef]
Hatfield, S.; Veszeleiova, K.; Steingold, J.; Sethuraman, J.; Sitkovsky, M. Mechanistic Justifications of Systemic Therapeutic Oxygenation of Tumors to Weaken the Hypoxia Inducible Factor 1α-Mediated Immunosuppression. Adv. Exp. Med. Biol. 2019, 1136, 113–121. [CrossRef] [PubMed]
Hatfield, S.M.; Kjaergaard, J.; Lukashev, D.; Schreiber, T.H.; Belikoff, B.; Abbott, R.; Sethumadhavan, S.; Philbrook, P.; Ko, K.; Cannici, R.; et al. Immunological Mechanisms of the Antitumor Effects of Supplemental Oxygenation. Sci. Transl. Med. 2015, 7, 277ra30. [CrossRef] [PubMed]
Eckert, F.; Zwirner, K.; Boeke, S.; Thorwarth, D.; Zips, D.; Huber, S.M. Rationale for Combining Radiotherapy and Immune Checkpoint Inhibition for Patients with Hypoxic Tumors. Front. Immunol. 2019, 10, 407. [CrossRef] [PubMed]
Dewhirst, M.W.; Mowery, Y.M.; Mitchell, J.B.; Cherukuri, M.K.; Secomb, T.W. Rationale for Hypoxia Assessment and Amelioration for Precision Therapy and Immunotherapy Studies. J. Clin. Investig. 2019, 129, 489–491. [CrossRef]
Carbone, F.; Grossi, F.; Bonaventura, A.; Vecchié, A.; Minetti, S.; Bardi, N.; Elia, E.; Ansaldo, A.M.; Ferrara, D.; Rijavec, E.; et al. Baseline Serum Levels of Osteopontin Predict Clinical Response to Treatment with Nivolumab in Patients with Non-Small Cell Lung Cancer. Clin. Exp. Metastasis 2019, 36, 449–456. [CrossRef] [PubMed]
Stieb, S.; Eleftheriou, A.; Warnock, G.; Guckenberger, M.; Riesterer, O. Longitudinal PET Imaging of Tumor Hypoxia during the Course of Radiotherapy. Eur. J. Nucl. Med. Mol. Imaging 2018, 45, 2201–2217. [CrossRef]
Eschmann, S.-M.; Paulsen, F.; Reimold, M.; Dittmann, H.; Welz, S.; Reischl, G.; Machulla, H.-J.; Bares, R. Prognostic Impact of Hypoxia Imaging with 18F-Misonidazole PET in Non-Small Cell Lung Cancer and Head and Neck Cancer before Radiotherapy. J. Nucl. Med. 2005, 46, 253–260. [PubMed]
Yang, Y.; Han, G.; Xu, W. The Diagnostic Value of 99TcM-2-(2-Methyl-5-Nitro-1H-Imidazol-1-Yl) Ethyl Dihydrogen Phosphate Hypoxia Imaging and Its Evaluation Performance for Radiotherapy Efficacy in Non-Small-Cell Lung Cancer. Onco Targets Ther. 2016, 9, 6499–6509. [CrossRef] [PubMed]
Watanabe, S.; Inoue, T.; Okamoto, S.; Magota, K.; Takayanagi, A.; Sakakibara-Konishi, J.; Katoh, N.; Hirata, K.; Manabe, O.; Toyonaga, T.; et al. Combination of FDG-PET and FMISO-PET as a Treatment Strategy for Patients Undergoing Early-Stage NSCLC Stereotactic Radiotherapy. EJNMMI Res. 2019, 9, 104. [CrossRef]
Li, L.; Yu, J.; Xing, L.; Ma, K.; Zhu, H.; Guo, H.; Sun, X.; Li, J.; Yang, G.; Li, W.; et al. Serial Hypoxia Imaging with 99mTc-HL91 SPECT to Predict Radiotherapy Response in Nonsmall Cell Lung Cancer. Am. J. Clin. Oncol. 2006, 29, 628–633. [CrossRef] [PubMed]
Grootjans, W.; de Geus-Oei, L.-F.; Bussink, J. Image-Guided Adaptive Radiotherapy in Patients with Locally Advanced Non-Small Cell Lung Cancer: The Art of PET. Q. J. Nucl. Med. Mol. Imaging 2018, 62, 369–384. [CrossRef]
Bollineni, V.R.; Wiegman, E.M.; Pruim, J.; Groen, H.J.M.; Langendijk, J.A. Hypoxia Imaging Using Positron Emission Tomography in Non-Small Cell Lung Cancer: Implications for Radiotherapy. Cancer Treat. Rev. 2012, 38, 1027–1032. [CrossRef] [PubMed]
Askoxylakis, V.; Dinkel, J.; Eichinger, M.; Stieltjes, B.; Sommer, G.; Strauss, L.G.; Dimitrakopoulou-Strauss, A.; Kopp-Schneider, A.; Haberkorn, U.; Huber, P.E.; et al. Multimodal Hypoxia Imaging and Intensity Modulated Radiation Therapy for Unresectable Non-Small-Cell Lung Cancer: The HIL Trial. Radiat. Oncol. 2012, 7, 157. [CrossRef]
Li, H.; Xu, D.; Han, X.; Ruan, Q.; Zhang, X.; Mi, Y.; Dong, M.; Guo, S.; Lin, Y.; Wang, B.; et al. Dosimetry Study of 18F-FMISO + PET/CT Hypoxia Imaging Guidance on Intensity-Modulated Radiation Therapy for Non-Small Cell Lung Cancer. Clin. Transl. Oncol. 2018, 20, 1329–1336. [CrossRef] [PubMed]
Horsman, M.R.; Mortensen, L.S.; Petersen, J.B.; Busk, M.; Overgaard, J. Imaging Hypoxia to Improve Radiotherapy Outcome. Nat. Rev. Clin. Oncol. 2012, 9, 674–687. [CrossRef] [PubMed]
Vera, P.; Mihailescu, S.-D.; Lequesne, J.; Modzelewski, R.; Bohn, P.; Hapdey, S.; Pépin, L.-F.; Dubray, B.; Chaumet-Riffaud, P.; Decazes, P.; et al. Radiotherapy Boost in Patients with Hypoxic Lesions Identified by 18F-FMISO PET/CT in Non-Small-Cell Lung Carcinoma: Can We Expect a Better Survival Outcome without Toxicity? [RTEP5 Long-Term Follow-Up]. Eur. J. Nucl. Med. Mol. Imaging 2019, 46, 1448–1456. [CrossRef]
Yang, L.; West, C.M. Hypoxia Gene Expression Signatures as Predictive Biomarkers for Personalising Radiotherapy. Br. J. Radiol. 2019, 92, 20180036. [CrossRef]
Peitzsch, C.; Perrin, R.; Hill, R.P.; Dubrovska, A.; Kurth, I. Hypoxia as a Biomarker for Radioresistant Cancer Stem Cells. Int. J. Radiat. Biol. 2014, 90, 636–652. [CrossRef]
Sørensen, B.S.; Horsman, M.R. Tumor Hypoxia: Impact on Radiation Therapy and Molecular Pathways. Front. Oncol. 2020, 10, 562. [CrossRef]
Moreno Roig, E.; Groot, A.J.; Yaromina, A.; Hendrickx, T.C.; Barbeau, L.M.O.; Giuranno, L.; Dams, G.; Ient, J.; Olivo Pimentel, V.; van Gisbergen, M.W.; et al. HIF-1α and HIF-2α Differently Regulate the Radiation Sensitivity of NSCLC Cells. Cells 2019, 8, 45. [CrossRef] [PubMed]
Harada, H. Hypoxia-Inducible Factor 1-Mediated Characteristic Features of Cancer Cells for Tumor Radioresistance. J. Radiat. Res. 2016, 57 (Suppl. 1), i99–i105. [CrossRef] [PubMed]
Gu, Q.; He, Y.; Ji, J.; Yao, Y.; Shen, W.; Luo, J.; Zhu, W.; Cao, H.; Geng, Y.; Xu, J.; et al. Hypoxia-Inducible Factor 1α (HIF-1α) and Reactive Oxygen Species (ROS) Mediates Radiation-Induced Invasiveness through the SDF-1α/CXCR4 Pathway in Non-Small Cell Lung Carcinoma Cells. Oncotarget 2015, 6, 10893–10907. [CrossRef] [PubMed]
Schilling, D.; Bayer, C.; Li, W.; Molls, M.; Vaupel, P.; Multhoff, G. Radiosensitization of Normoxic and Hypoxic H1339 Lung Tumor Cells by Heat Shock Protein 90 Inhibition Is Independent of Hypoxia Inducible Factor-1α. PLoS ONE 2012, 7, e31110. [CrossRef] [PubMed]
Kim, W.-Y.; Oh, S.H.; Woo, J.-K.; Hong, W.K.; Lee, H.-Y. Targeting Heat Shock Protein 90 Overrides the Resistance of Lung Cancer Cells by Blocking Radiation-Induced Stabilization of Hypoxia-Inducible Factor-1alpha. Cancer Res. 2009, 69, 1624–1632. [CrossRef] [PubMed]
Devlin, C.; Greco, S.; Martelli, F.; Ivan, M. MiR-210: More than a Silent Player in Hypoxia. IUBMB Life 2011, 63, 94–100. [CrossRef]
Grosso, S.; Doyen, J.; Parks, S.K.; Bertero, T.; Paye, A.; Cardinaud, B.; Gounon, P.; Lacas-Gervais, S.; Noël, A.; Pouysségur, J.; et al. MiR-210 Promotes a Hypoxic Phenotype and Increases Radioresistance in Human Lung Cancer Cell Lines. Cell Death Dis. 2013, 4, e544. [CrossRef] [PubMed]
Saki, M.; Makino, H.; Javvadi, P.; Tomimatsu, N.; Ding, L.-H.; Clark, J.E.; Gavin, E.; Takeda, K.; Andrews, J.; Saha, D.; et al. EGFR Mutations Compromise Hypoxia-Associated Radiation Resistance through Impaired Replication Fork-Associated DNA Damage Repair. Mol. Cancer Res. 2017, 15, 1503–1516. [CrossRef]
Yang, H.; Liang, S.-Q.; Schmid, R.A.; Peng, R.-W. New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness. Front. Oncol. 2019, 9, 953. [CrossRef]
Aran, V.; Omerovic, J. Current Approaches in NSCLC Targeting K-RAS and EGFR. Int. J. Mol. Sci. 2019, 20, 5701. [CrossRef]
De la Garza, M.M.; Cumpian, A.M.; Daliri, S.; Castro-Pando, S.; Umer, M.; Gong, L.; Khosravi, N.; Caetano, M.S.; Ramos-Castañeda, M.; Flores, A.G.; et al. COPD-Type Lung Inflammation Promotes K-Ras Mutant Lung Cancer through Epithelial HIF-1α Mediated Tumor Angiogenesis and Proliferation. Oncotarget 2018, 9, 32972–32983. [CrossRef] [PubMed]
Gong, L.; da Silva Caetano, M.; Cumpian, A.M.; Daliri, S.; Garza Flores, A.; Chang, S.H.; Ochoa, C.E.; Evans, C.M.; Yu, Z.; Moghaddam, S.J. Tumor Necrosis Factor Links Chronic Obstructive Pulmonary Disease and K-Ras Mutant Lung Cancer through Induction of an Immunosuppressive pro-Tumor Microenvironment. Oncoimmunology 2016, 5, e1229724. [CrossRef] [PubMed]
Deng, S.; Clowers, M.J.; Velasco, W.V.; Ramos-Castaneda, M.; Moghaddam, S.J. Understanding the Complexity of the Tumor Microenvironment in K-Ras Mutant Lung Cancer: Finding an Alternative Path to Prevention and Treatment. Front. Oncol. 2019, 9, 1556. [CrossRef]
Yoshikawa, Y.; Takano, O.; Kato, I.; Takahashi, Y.; Shima, F.; Kataoka, T. Ras Inhibitors Display an Anti-Metastatic Effect by Downregulation of Lysyl Oxidase through Inhibition of the Ras-PI3K-Akt-HIF-1α Pathway. Cancer Lett. 2017, 410, 82–91. [CrossRef] [PubMed]
Orue, A.; Chavez, V.; Strasberg-Rieber, M.; Rieber, M. Hypoxic Resistance of KRAS Mutant Tumor Cells to 3-Bromopyruvate Is Counteracted by Prima-1 and Reversed by N-Acetylcysteine. BMC Cancer 2016, 16, 902. [CrossRef] [PubMed]
Wu, S.-G.; Shih, J.-Y. Management of Acquired Resistance to EGFR TKI-Targeted Therapy in Advanced Non-Small Cell Lung Cancer. Mol. Cancer 2018, 17, 38. [CrossRef]
Shepherd, F.A.; Rodrigues Pereira, J.; Ciuleanu, T.; Tan, E.H.; Hirsh, V.; Thongprasert, S.; Campos, D.; Maoleekoonpiroj, S.; Smylie, M.; Martins, R.; et al. Erlotinib in Previously Treated Non–Small-Cell Lung Cancer. N. Engl. J. Med. 2005, 353, 123–132. [CrossRef]
Pore, N.; Jiang, Z.; Gupta, A.; Cerniglia, G.; Kao, G.D.; Maity, A. EGFR Tyrosine Kinase Inhibitors Decrease VEGF Expression by Both Hypoxia-Inducible Factor (HIF)-1-Independent and HIF-1-Dependent Mechanisms. Cancer Res. 2006, 66, 3197–3204. [CrossRef] [PubMed]
An, S.-M.; Lei, H.-M.; Ding, X.-P.; Sun, F.; Zhang, C.; Tang, Y.-B.; Chen, H.-Z.; Shen, Y.; Zhu, L. Interleukin-6 Identified as an Important Factor in Hypoxia-and Aldehyde Dehydrogenase-Based Gefitinib Adaptive Resistance in Non-Small Cell Lung Cancer Cells. Oncol. Lett. 2017, 14, 3445–3454. [CrossRef] [PubMed]
Park, S.; Ha, S.Y.; Cho, H.Y.; Chung, D.H.; Kim, N.R.; Hong, J.; Cho, E.K. Prognostic Implications of Hypoxia-Inducible Factor-1α in Epidermal Growth Factor Receptor-Negative Non-Small Cell Lung Cancer. Lung Cancer 2011, 72, 100–107. [CrossRef] [PubMed]
Minakata, K.; Takahashi, F.; Nara, T.; Hashimoto, M.; Tajima, K.; Murakami, A.; Nurwidya, F.; Yae, S.; Koizumi, F.; Moriyama, H.; et al. Hypoxia Induces Gefitinib Resistance in Non-Small-Cell Lung Cancer with Both Mutant and Wild-Type Epidermal Growth Factor Receptors. Cancer Sci. 2012, 103, 1946–1954. [CrossRef] [PubMed]
Lu, Y.; Liang, K.; Li, X.; Fan, Z. Responses of Cancer Cells with Wild-Type or Tyrosine Kinase Domain-Mutated Epidermal Growth Factor Receptor (EGFR) to EGFR-Targeted Therapy Are Linked to Downregulation of Hypoxia-Inducible Factor-1alpha. Mol. Cancer 2007, 6, 63. [CrossRef] [PubMed]
Jin, Q.; Zhou, J.; Xu, X.; Huang, F.; Xu, W. Hypoxia-Inducible Factor-1 Signaling Pathway Influences the Sensitivity of HCC827 Cells to Gefitinib. Oncol. Lett. 2019, 17, 4034–4043. [CrossRef] [PubMed]
Xu, L.; Nilsson, M.B.; Saintigny, P.; Cascone, T.; Herynk, M.H.; Du, Z.; Nikolinakos, P.G.; Yang, Y.; Prudkin, L.; Liu, D.; et al. Epidermal Growth Factor Receptor Regulates MET Levels and Invasiveness through Hypoxia-Inducible Factor-1a in Non-Small Cell Lung Cancer Cells. Oncogene 2010, 29, 2616–2627. [CrossRef] [PubMed]
Murakami, A.; Takahashi, F.; Nurwidya, F.; Kobayashi, I.; Minakata, K.; Hashimoto, M.; Nara, T.; Kato, M.; Tajima, K.; Shimada, N.; et al. Hypoxia Increases Gefitinib-Resistant Lung Cancer Stem Cells through the Activation of Insulin-like Growth Factor 1 Receptor. PLoS ONE 2014, 9, e86459. [CrossRef] [PubMed]
Lu, Y.; Liu, Y.; Oeck, S.; Glazer, P.M. Hypoxia Promotes Resistance to EGFR Inhibition in NSCLC Cells via the Histone Demethylases, LSD1 and PLU-1. Mol. Cancer Res. 2018, 16, 1458–1469. [CrossRef]
Kani, K.; Garri, C.; Tiemann, K.; Malihi, P.D.; Punj, V.; Nguyen, A.L.; Lee, J.; Hughes, L.D.; Alvarez, R.M.; Wood, D.M.; et al. JUN-Mediated Downregulation of EGFR Signaling Is Associated with Resistance to Gefitinib in EGFR-Mutant NSCLC Cell Lines. Mol. Cancer Ther. 2017, 16, 1645–1657. [CrossRef]
Chen, Z.; Tian, D.; Liao, X.; Zhang, Y.; Xiao, J.; Chen, W.; Liu, Q.; Chen, Y.; Li, D.; Zhu, L.; et al. Apigenin Combined With Gefitinib Blocks Autophagy Flux and Induces Apoptotic Cell Death Through Inhibition of HIF-1α, c-Myc, p-EGFR, and Glucose Metabolism in EGFR L858R+T790M-Mutated H1975 Cells. Front. Pharmacol. 2019, 10, 260. [CrossRef] [PubMed]
Kobayashi, M.; Saito, R.; Miki, Y.; Nanamiya, R.; Inoue, C.; Abe, J.; Sato, I.; Okada, Y.; Sasano, H. The Correlation of P22phox and Chemosensitivity in EGFR-TKI Resistant Lung Adenocarcinoma. Oncotarget 2019, 10, 1119–1131. [CrossRef] [PubMed]
Lee, J.G.; Wu, R. Erlotinib-Cisplatin Combination Inhibits Growth and Angiogenesis through c-MYC and HIF-1α in EGFR-Mutated Lung Cancer in Vitro and in Vivo. Neoplasia 2015, 17, 190–200. [CrossRef] [PubMed]
Saito, H.; Fukuhara, T.; Furuya, N.; Watanabe, K.; Sugawara, S.; Iwasawa, S.; Tsunezuka, Y.; Yamaguchi, O.; Okada, M.; Yoshimori, K.; et al. Erlotinib plus Bevacizumab versus Erlotinib Alone in Patients with EGFR-Positive Advanced Non-Squamous Non-Small-Cell Lung Cancer (NEJ026). Lancet Oncol. 2019, 20, 625–635. [CrossRef]
Ninomiya, T.; Ishikawa, N.; Inoue, K.; Kubo, T.; Yasugi, M.; Shibayama, T.; Maeda, T.; Fujitaka, K.; Kodani, M.; Yokoyama, T.; et al. Phase 2 Study of Afatinib Alone or Combined with Bevacizumab in Chemonaive Patients With Advanced Non-Small-Cell Lung Cancer Harboring EGFR Mutations: AfaBev-CS Study Protocol. Clin. Lung Cancer 2019, 20, 134–138. [CrossRef] [PubMed]
Hu, H.; Miao, X.-K.; Li, J.-Y.; Zhang, X.-W.; Xu, J.-J.; Zhang, J.-Y.; Zhou, T.-X.; Hu, M.-N.; Yang, W.-L.; Mou, L.-Y. YC-1 Potentiates the Antitumor Activity of Gefitinib by Inhibiting HIF-1α and Promoting the Endocytic Trafficking and Degradation of EGFR in Gefitinib-Resistant Non-Small-Cell Lung Cancer Cells. Eur. J. Pharmacol. 2020, 874, 172961. [CrossRef] [PubMed]
Li, F.; Mei, H.; Gao, Y.; Xie, X.; Nie, H.; Li, T.; Zhang, H.; Jia, L. Co-Delivery of Oxygen and Erlotinib by Aptamer-Modified Liposomal Complexes to Reverse Hypoxia-Induced Drug Resistance in Lung Cancer. Biomaterials 2017, 145, 56–71. [CrossRef]
Du, X.; Shao, Y.; Qin, H.-F.; Tai, Y.-H.; Gao, H.-J. ALK-Rearrangement in Non-Small-Cell Lung Cancer (NSCLC). Thorac. Cancer 2018, 9, 423–430. [CrossRef]
Martinengo, C.; Poggio, T.; Menotti, M.; Scalzo, M.S.; Mastini, C.; Ambrogio, C.; Pellegrino, E.; Riera, L.; Piva, R.; Ribatti, D.; et al. ALK-Dependent Control of Hypoxia-Inducible Factors Mediates Tumor Growth and Metastasis. Cancer Res. 2014, 74, 6094–6106. [CrossRef]
Sharma, G.G.; Mota, I.; Mologni, L.; Patrucco, E.; Gambacorti-Passerini, C.; Chiarle, R. Tumor Resistance against ALK Targeted Therapy-Where It Comes from and Where It Goes. Cancers 2018, 10, 62. [CrossRef]
Ma, Y.; Yu, C.; Mohamed, E.M.; Shao, H.; Wang, L.; Sundaresan, G.; Zweit, J.; Idowu, M.; Fang, X. A Causal Link from ALK to Hexokinase II Overexpression and Hyperactive Glycolysis in EML4-ALK-Positive Lung Cancer. Oncogene 2016, 35, 6132–6142. [CrossRef] [PubMed]
Kogita, A.; Togashi, Y.; Hayashi, H.; Sogabe, S.; Terashima, M.; De Velasco, M.A.; Sakai, K.; Fujita, Y.; Tomida, S.; Takeyama, Y.; et al. Hypoxia Induces Resistance to ALK Inhibitors in the H3122 Non-Small Cell Lung Cancer Cell Line with an ALK Rearrangement via Epithelial-Mesenchymal Transition. Int. J. Oncol. 2014, 45, 1430–1436. [CrossRef] [PubMed]
Koh, J.; Jang, J.-Y.; Keam, B.; Kim, S.; Kim, M.-Y.; Go, H.; Kim, T.M.; Kim, D.-W.; Kim, C.-W.; Jeon, Y.K.; et al. EML4-ALK Enhances Programmed Cell Death-Ligand 1 Expression in Pulmonary Adenocarcinoma via Hypoxia-Inducible Factor (HIF)-1α and STAT3. Oncoimmunology 2016, 5, e1108514. [CrossRef] [PubMed]
Bielec, B.; Schueffl, H.; Terenzi, A.; Berger, W.; Heffeter, P.; Keppler, B.K.; Kowol, C.R. Development and Biological Investigations of Hypoxia-Sensitive Prodrugs of the Tyrosine Kinase Inhibitor Crizotinib. Bioorg. Chem. 2020, 99, 103778. [CrossRef] [PubMed]
Denko, N.C. Hypoxia, HIF1 and Glucose Metabolism in the Solid Tumour. Nat. Rev. Cancer 2008, 8, 705–713. [CrossRef]
Kim, J.; Tchernyshyov, I.; Semenza, G.L.; Dang, C.V. HIF-1-Mediated Expression of Pyruvate Dehydrogenase Kinase: A Metabolic Switch Required for Cellular Adaptation to Hypoxia. Cell Metab. 2006, 3, 177–185. [CrossRef] [PubMed]
Yang, R.; Guo, C. Discovery of Potent Pyruvate Dehydrogenase Kinase Inhibitors and Evaluation of Their Anti-Lung Cancer Activity under Hypoxia. Medchemcomm 2018, 9, 1843–1849. [CrossRef] [PubMed]
Liu, T.; Yin, H. PDK1 Promotes Tumor Cell Proliferation and Migration by Enhancing the Warburg Effect in Non-Small Cell Lung Cancer. Oncol. Rep. 2017, 37, 193–200. [CrossRef] [PubMed]
Yang, Z.; Tam, K.Y. Anti-Cancer Synergy of Dichloroacetate and EGFR Tyrosine Kinase Inhibitors in NSCLC Cell Lines. Eur. J. Pharmacol. 2016, 789, 458–467. [CrossRef]
Yang, Z.; Hu, X.; Zhang, S.; Zhang, W.; Tam, K.Y. Pharmacological Synergism of 2,2-Dichloroacetophenone and EGFR-TKi to Overcome TKi-Induced Resistance in NSCLC Cells. Eur. J. Pharmacol. 2017, 815, 80–87. [CrossRef] [PubMed]
Romero, Y.; Castillejos-López, M.; Romero-García, S.; Aguayo, A.S.; Herrera, I.; Garcia-Martin, M.O.; Torres-Espíndola, L.M.; Negrete-García, M.C.; Olvera, A.C.; Huerta-Cruz, J.C.; et al. Antitumor Therapy under Hypoxic Microenvironment by the Combination of 2-Methoxyestradiol and Sodium Dichloroacetate on Human Non-Small-Cell Lung Cancer. Oxid. Med. Cell. Longev. 2020, 2020, 3176375. [CrossRef]
Garon, E.B.; Christofk, H.R.; Hosmer, W.; Britten, C.D.; Bahng, A.; Crabtree, M.J.; Hong, C.S.; Kamranpour, N.; Pitts, S.; Kabbinavar, F.; et al. Dichloroacetate Should Be Considered with Platinum-Based Chemotherapy in Hypoxic Tumors rather than as a Single Agent in Advanced Non-Small Cell Lung Cancer. J. Cancer Res. Clin. Oncol. 2014, 140, 443–452. [CrossRef] [PubMed]
Yang, Z.; Zhang, S.-L.; Hu, X.; Tam, K.Y. Inhibition of Pyruvate Dehydrogenase Kinase 1 Enhances the Anti-Cancer Effect of EGFR Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer. Eur. J. Pharmacol. 2018, 838, 41–52. [CrossRef] [PubMed]
Zahra, K.; Dey, T.; Ashish; Mishra, S.P.; Pandey, U. Pyruvate Kinase M2 and Cancer: The Role of PKM2 in Promoting Tumorigene-sis. Front. Oncol. 2020, 10, 159. [CrossRef]
Guo, C.-Y.; Zhu, Q.; Tou, F.-F.; Wen, X.-M.; Kuang, Y.-K.; Hu, H. The Prognostic Value of PKM2 and Its Correlation with Tumour Cell PD-L1 in Lung Adenocarcinoma. BMC Cancer 2019, 19, 289. [CrossRef]
Su, Q.; Luo, S.; Tan, Q.; Deng, J.; Zhou, S.; Peng, M.; Tao, T.; Yang, X. The Role of Pyruvate Kinase M2 in Anticancer Therapeutic Treatments. Oncol. Lett. 2019, 18, 5663–5672. [CrossRef] [PubMed]
Chun, S.G.; Liao, Z.; Jeter, M.D.; Chang, J.Y.; Lin, S.H.; Komaki, R.U.; Guerrero, T.M.; Mayo, R.C.; Korah, B.M.; Koshy, S.M.; et al. Metabolic Responses to Metformin in Inoperable Early-Stage Non-Small Cell Lung Cancer Treated with Stereotactic Radiotherapy: Results of a Randomized Phase II Clinical Trial. Am. J. Clin. Oncol. 2020, 43, 231–235. [CrossRef]
Kubo, T.; Ninomiya, T.; Hotta, K.; Kozuki, T.; Toyooka, S.; Okada, H.; Fujiwara, T.; Udono, H.; Kiura, K. Study Protocol: Phase-Ib Trial of Nivolumab Combined with Metformin for Refractory/Recurrent Solid Tumors. Clin. Lung Cancer 2018, 19, e861–e864. [CrossRef]
Afzal, M.Z.; Dragnev, K.; Sarwar, T.; Shirai, K. Clinical Outcomes in Non-Small-Cell Lung Cancer Patients Receiving Concurrent Metformin and Immune Checkpoint Inhibitors. Lung Cancer Manag. 2019, 8, LMT11. [CrossRef]
Ahmed, I.; Ferro, A.; Cohler, A.; Langenfeld, J.; Surakanti, S.G.; Aisner, J.; Zou, W.; Haffty, B.G.; Jabbour, S.K. Impact of Metformin Use on Survival in Locally-Advanced, Inoperable Non-Small Cell Lung Cancer Treated with Definitive Chemoradiation. J. Thorac. Dis. 2015, 7, 346–355. [CrossRef]
Stang, K.; Alite, F.; Adams, W.; Altoos, B.; Small, C.; Melian, E.; Emami, B.; Harkenrider, M. Impact of Concurrent Coincident Use of Metformin During Lung Stereotactic Body Radiation Therapy. Cureus 2021, 13, e14157. [CrossRef]
Wink, K.C.J.; Belderbos, J.S.A.; Dieleman, E.M.T.; Rossi, M.; Rasch, C.R.N.; Damhuis, R.A.M.; Houben, R.M.A.; Troost, E.G.C. Improved Progression Free Survival for Patients with Diabetes and Locally Advanced Non-Small Cell Lung Cancer (NSCLC) Using Metformin during Concurrent Chemoradiotherapy. Radiother. Oncol. 2016, 118, 453–459. [CrossRef]
Brancher, S.; Støer, N.C.; Weiderpass, E.; Damhuis, R.A.M.; Johannesen, T.B.; Botteri, E.; Strand, T.-E. Metformin Use and Lung Cancer Survival: A Population-Based Study in Norway. Br. J. Cancer 2021, 124, 1018–1025. [CrossRef]
Li, L.; Jiang, L.; Wang, Y.; Zhao, Y.; Zhang, X.-J.; Wu, G.; Zhou, X.; Sun, J.; Bai, J.; Ren, B.; et al. Combination of Metformin and Gefitinib as First-Line Therapy for Nondiabetic Advanced NSCLC Patients with EGFR Mutations: A Randomized, Double-Blind Phase II Trial. Clin. Cancer Res. 2019, 25, 6967–6975. [CrossRef] [PubMed]
Zhang, B.; Xie, Z.; Li, B. The Clinicopathologic Impacts and Prognostic Significance of GLUT1 Expression in Patients with Lung Cancer: A Meta-Analysis. Gene 2019, 689, 76–83. [CrossRef]
Shriwas, P.; Roberts, D.; Li, Y.; Wang, L.; Qian, Y.; Bergmeier, S.; Hines, J.; Adhicary, S.; Nielsen, C.; Chen, X. A Small-Molecule Pan-Class I Glucose Transporter Inhibitor Reduces Cancer Cell Proliferation in Vitro and Tumor Growth in Vivo by Targeting Glucose-Based Metabolism. Cancer Metab. 2021, 9, 14. [CrossRef] [PubMed]
Hutt, D.M.; Roth, D.M.; Vignaud, H.; Cullin, C.; Bouchecareilh, M. The Histone Deacetylase Inhibitor, Vorinostat, Represses Hypoxia Inducible Factor 1 Alpha Expression through Translational Inhibition. PLoS ONE 2014, 9, e106224. [CrossRef] [PubMed]
Traynor, A.M.; Dubey, S.; Eickhoff, J.C.; Kolesar, J.M.; Schell, K.; Huie, M.S.; Groteluschen, D.L.; Marcotte, S.M.; Hallahan, C.M.; Weeks, H.R.; et al. Vorinostat (NSC# 701852) in Patients with Relapsed Non-Small Cell Lung Cancer: A Wisconsin Oncology Network Phase II Study. J. Thorac. Oncol. 2009, 4, 522–526. [CrossRef] [PubMed]
Krug, L.M.; Kindler, H.L.; Calvert, H.; Manegold, C.; Tsao, A.S.; Fennell, D.; Öhman, R.; Plummer, R.; Eberhardt, W.E.E.; Fukuoka, K.; et al. Vorinostat in Patients with Advanced Malignant Pleural Mesothelioma Who Have Progressed on Previous Chemotherapy (VANTAGE-014): A Phase 3, Double-Blind, Randomised, Placebo-Controlled Trial. Lancet Oncol. 2015, 16, 447–456. [CrossRef]
Vansteenkiste, J.; Van Cutsem, E.; Dumez, H.; Chen, C.; Ricker, J.L.; Randolph, S.S.; Schöffski, P. Early Phase II Trial of Oral Vorinostat in Relapsed or Refractory Breast, Colorectal, or Non-Small Cell Lung Cancer. Investig. New Drugs 2008, 26, 483–488. [CrossRef]
Ramalingam, S.S.; Maitland, M.L.; Frankel, P.; Argiris, A.E.; Koczywas, M.; Gitlitz, B.; Thomas, S.; Espinoza-Delgado, I.; Vokes, E.E.; Gandara, D.R.; et al. Carboplatin and Paclitaxel in Combination with either Vorinostat or Placebo for First-Line Therapy of Advanced Non-Small-Cell Lung Cancer. J. Clin. Oncol. 2010, 28, 56–62. [CrossRef]
Choi, C.Y.H.; Wakelee, H.A.; Neal, J.W.; Pinder-Schenck, M.C.; Yu, H.-H.M.; Chang, S.D.; Adler, J.R.; Modlin, L.A.; Harsh, G.R.; Soltys, S.G. Vorinostat and Concurrent Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases: A Phase 1 Dose Escalation Trial. Int. J. Radiat. Oncol. Biol. Phys. 2017, 99, 16–21. [CrossRef] [PubMed]
Reguart, N.; Rosell, R.; Cardenal, F.; Cardona, A.F.; Isla, D.; Palmero, R.; Moran, T.; Rolfo, C.; Pallarès, M.C.; Insa, A.; et al. Phase I/II Trial of Vorinostat (SAHA) and Erlotinib for Non-Small Cell Lung Cancer (NSCLC) Patients with Epidermal Growth Factor Receptor (EGFR) Mutations after Erlotinib Progression. Lung Cancer 2014, 84, 161–167. [CrossRef]
Han, J.-Y.; Lee, S.H.; Lee, G.K.; Yun, T.; Lee, Y.J.; Hwang, K.H.; Kim, J.Y.; Kim, H.T. Phase I/II Study of Gefitinib (Iressa® ) and Vorinostat (IVORI) in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer. Cancer Chemother. Pharmacol. 2015, 75, 475–483. [CrossRef]
Takeuchi, S.; Hase, T.; Shimizu, S.; Ando, M.; Hata, A.; Murakami, H.; Kawakami, T.; Nagase, K.; Yoshimura, K.; Fujiwara, T.; et al. Phase I Study of Vorinostat with Gefitinib in BIM Deletion Polymorphism/Epidermal Growth Factor Receptor Mutation Double-Positive Lung Cancer. Cancer Sci. 2020, 111, 561–570. [CrossRef] [PubMed]
Gray, J.E.; Saltos, A.; Tanvetyanon, T.; Haura, E.B.; Creelan, B.; Antonia, S.J.; Shafique, M.; Zheng, H.; Dai, W.; Saller, J.J.; et al. Phase I/Ib Study of Pembrolizumab Plus Vorinostat in Advanced/Metastatic Non-Small Cell Lung Cancer. Clin. Cancer Res. 2019, 25, 6623–6632. [CrossRef] [PubMed]
Yasuda, H.; Yamaya, M.; Nakayama, K.; Sasaki, T.; Ebihara, S.; Kanda, A.; Asada, M.; Inoue, D.; Suzuki, T.; Okazaki, T.; et al. Randomized Phase II Trial Comparing Nitroglycerin plus Vinorelbine and Cisplatin with Vinorelbine and Cisplatin Alone in Previously Untreated Stage IIIB/IV Non-Small-Cell Lung Cancer. J. Clin. Oncol. 2006, 24, 688–694. [CrossRef]
Dingemans, A.-M.C.; Groen, H.J.M.; Herder, G.J.M.; Stigt, J.A.; Smit, E.F.; Bahce, I.; Burgers, J.A.; van den Borne, B.E.E.M.; Biesma, B.; Vincent, A.; et al. A Randomized Phase II Study Comparing Paclitaxel-Carboplatin-Bevacizumab with or without Nitroglycerin Patches in Patients with Stage IV Nonsquamous Nonsmall-Cell Lung Cancer: NVALT12 (NCT01171170). Ann. Oncol. 2015, 26, 2286–2293. [CrossRef]
Davidson, A.; Veillard, A.-S.; Tognela, A.; Chan, M.M.K.; Hughes, B.G.M.; Boyer, M.; Briscoe, K.; Begbie, S.; Abdi, E.; Crombie, C.; et al. A Phase III Randomized Trial of Adding Topical Nitroglycerin to First-Line Chemotherapy for Advanced Nonsmall-Cell Lung Cancer: The Australasian Lung Cancer Trials Group NITRO Trial. Ann. Oncol. 2015, 26, 2280–2286. [CrossRef]
Reymen, B.J.T.; van Gisbergen, M.W.; Even, A.J.G.; Zegers, C.M.L.; Das, M.; Vegt, E.; Wildberger, J.E.; Mottaghy, F.M.; Yaromina, A.; Dubois, L.J.; et al. Nitroglycerin as a Radiosensitizer in Non-Small Cell Lung Cancer: Results of a Prospective Imaging-Based Phase II Trial. Clin. Transl. Radiat. Oncol. 2020, 21, 49–55. [CrossRef]
von Pawel, J.; von Roemeling, R.; Gatzemeier, U.; Boyer, M.; Elisson, L.O.; Clark, P.; Talbot, D.; Rey, A.; Butler, T.W.; Hirsh, V.; et al. Tirapazamine plus Cisplatin versus Cisplatin in Advanced Non-Small-Cell Lung Cancer: A Report of the International CATAPULT I Study Group. Cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors. J. Clin. Oncol. 2000, 18, 1351–1359. [CrossRef]
Huang, W.; Zeng, Y.C. A Candidate for Lung Cancer Treatment: Arsenic Trioxide. Clin. Transl. Oncol. 2019, 21, 1115–1126. [CrossRef]
Choy, H.; Nabid, A.; Stea, B.; Scott, C.; Roa, W.; Kleinberg, L.; Ayoub, J.; Smith, C.; Souhami, L.; Hamburg, S.; et al. Phase II Multicenter Study of Induction Chemotherapy Followed by Concurrent Efaproxiral (RSR13) and Thoracic Radiotherapy for Patients with Locally Advanced Non-Small-Cell Lung Cancer. J. Clin. Oncol. 2005, 23, 5918–5928. [CrossRef] [PubMed]
Suh, J.H.; Stea, B.; Nabid, A.; Kresl, J.J.; Fortin, A.; Mercier, J.-P.; Senzer, N.; Chang, E.L.; Boyd, A.P.; Cagnoni, P.J.; et al. Phase III Study of Efaproxiral as an Adjunct to Whole-Brain Radiation Therapy for Brain Metastases. J. Clin. Oncol. 2006, 24, 106–114. [CrossRef] [PubMed]
McGowan, D.R.; Skwarski, M.; Bradley, K.M.; Campo, L.; Fenwick, J.D.; Gleeson, F.V.; Green, M.; Horne, A.; Maughan, T.S.; McCole, M.G.; et al. Buparlisib with Thoracic Radiotherapy and Its Effect on Tumour Hypoxia: A Phase I Study in Patients with Advanced Non-Small Cell Lung Carcinoma. Eur. J. Cancer 2019, 113, 87–95. [CrossRef] [PubMed]
Kabakov, A.E.; Yakimova, A.O. Hypoxia-Induced Cancer Cell Responses Driving Radioresistance of Hypoxic Tumors: Approaches to Targeting and Radiosensitizing. Cancers 2021, 13, 1102. [CrossRef]
Tubin, S.; Khan, M.K.; Salerno, G.; Mourad, W.F.; Yan, W.; Jeremic, B. Mono-Institutional Phase 2 Study of Innovative Stereotactic Body RadioTherapy Targeting PArtial Tumor HYpoxic (SBRT-PATHY) Clonogenic Cells in Unresectable Bulky Non-Small Cell Lung Cancer: Profound Non-Targeted Effects by Sparing Peri-Tumoral Immune Microenvironment. Radiat. Oncol. 2019, 14, 212. [CrossRef]
Tubin, S.; Gupta, S.; Grusch, M.; Popper, H.H.; Brcic, L.; Ashdown, M.L.; Khleif, S.N.; Peter-Vörösmarty, B.; Hyden, M.; Negrini, S.; et al. Shifting the Immune-Suppressive to Predominant Immune-Stimulatory Radiation Effects by SBRT-PArtial Tumor Irradiation Targeting HYpoxic Segment (SBRT-PATHY). Cancers 2020, 13, 50. [CrossRef]
Garcia, J.; Hurwitz, H.I.; Sandler, A.B.; Miles, D.; Coleman, R.L.; Deurloo, R.; Chinot, O.L. Bevacizumab (Avastin® ) in Cancer Treatment: A Review of 15 Years of Clinical Experience and Future Outlook. Cancer Treat. Rev. 2020, 86, 102017. [CrossRef]
Shukla, N.A.; Yan, M.N.; Hanna, N. The Story of Angiogenesis Inhibitors in Non-Small-Cell Lung Cancer: The Past, Present, and Future. Clin. Lung Cancer 2020. [CrossRef]
Qiang, H.; Chang, Q.; Xu, J.; Qian, J.; Zhang, Y.; Lei, Y.; Han, B.; Chu, T. New Advances in Antiangiogenic Combination Therapeutic Strategies for Advanced Non-Small Cell Lung Cancer. J. Cancer Res. Clin. Oncol. 2020, 146, 631–645. [CrossRef] [PubMed]
Cantelmo, A.R.; Dejos, C.; Kocher, F.; Hilbe, W.; Wolf, D.; Pircher, A. Angiogenesis Inhibition in Non-Small Cell Lung Cancer: A Critical Appraisal, Basic Concepts and Updates from American Society for Clinical Oncology 2019. Curr. Opin. Oncol. 2020, 32, 44–53. [CrossRef] [PubMed]
Manegold, C.; Dingemans, A.-M.C.; Gray, J.E.; Nakagawa, K.; Nicolson, M.; Peters, S.; Reck, M.; Wu, Y.-L.; Brustugun, O.T.; Crinò, L.; et al. The Potential of Combined Immunotherapy and Antiangiogenesis for the Synergistic Treatment of Advanced NSCLC. J. Thorac. Oncol. 2017, 12, 194–207. [CrossRef] [PubMed]
Shiraishi, Y.; Kishimoto, J.; Tanaka, K.; Sugawara, S.; Daga, H.; Hirano, K.; Azuma, K.; Hataji, O.; Hayashi, H.; Tachihara, M.; et al. Treatment Rationale and Design for APPLE (WJOG11218L): A Multicenter, Open-Label, Randomized Phase 3 Study of Ate-zolizumab and Platinum/Pemetrexed With or Without Bevacizumab for Patients with Advanced Nonsquamous Non-Small-Cell Lung Cancer. Clin. Lung Cancer 2020, 21, 472–476. [CrossRef] [PubMed]
Taylor, M.H.; Lee, C.-H.; Makker, V.; Rasco, D.; Dutcus, C.E.; Wu, J.; Stepan, D.E.; Shumaker, R.C.; Motzer, R.J. Phase IB/II Trial of Lenvatinib Plus Pembrolizumab in Patients with Advanced Renal Cell Carcinoma, Endometrial Cancer, and Other Selected Advanced Solid Tumors. J. Clin. Oncol. 2020, 38, 1154–1163. [CrossRef]
Nishio, M.; Horai, T.; Horiike, A.; Nokihara, H.; Yamamoto, N.; Takahashi, T.; Murakami, H.; Yamamoto, N.; Koizumi, F.; Nishio, K.; et al. Phase 1 Study of Lenvatinib Combined with Carboplatin and Paclitaxel in Patients with Non-Small-Cell Lung Cancer. Br. J. Cancer 2013, 109, 538–544. [CrossRef]
