F. Martínez-Jiménez et al. A compendium of mutational cancer driver genes Nat. Rev. Cancer 2020 20 555 572 32778778
J.M. Ostrem U. Peters M.L. Sos J.A. Wells K.M. Shokat K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions Nature 2013 503 548 551 2013Natur.503.548O 1:CAS:528:DC%2BC3sXhvVGqs7jO 24256730 4274051
F. Skoulidis et al. Sotorasib for lung cancers with KRAS p.G12C mutation N. Engl. J. Med. 2021 384 2371 2381 1:CAS:528:DC%2BB3MXhsVSrtL3N 34096690 9116274
J. Canon et al. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity Nature 2019 575 217 223 2019Natur.575.217C 1:CAS:528:DC%2BC1MXitV2hsb7F 31666701
Riely, G. J. et al. 99O_PR KRYSTAL-1: activity and preliminary pharmacodynamic (PD) analysis of adagrasib (MRTX849) in patients (Pts) with advanced non–small cell lung cancer (NSCLC) harboring KRASG12C mutation. J. Thorac. Oncol. 16, S751–S752 (2021).
J.B. Fell et al. Identification of the clinical development candidate MRTX849, a covalent KRASG12C inhibitor for the treatment of cancer J. Med. Chem. 2020 63 6679 6693 1:CAS:528:DC%2BB3cXmtlCntb4%3D 32250617
N. Perurena L. Situ K. Cichowski Combinatorial strategies to target RAS-driven cancers Nat. Rev. Cancer 2024 24 316 337 1:CAS:528:DC%2BB2cXosFOqtr8%3D 38627557
A. de Langen et al. Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRASG12C mutation: a randomised, open-label, phase 3 trial Lancet 2023 401 733 746 36764316
D.S. Hong et al. KRAS-G12C inhibition with sotorasib in advanced solid tumors N. Engl. J. Med. 2020 383 1207 1217 1:CAS:528:DC%2BB3cXhvFalu7rL 32955176 7571518
M.M. Awad et al. Acquired resistance to KRAS G12C inhibition in cancer N. Engl. J. Med. 2021 384 2382 2393 1:CAS:528:DC%2BB3MXhsVSrtL3J 34161704 8864540
J.Y. Xue et al. Rapid non-uniform adaptation to conformation-specific KRAS(G12C) inhibition Nature 2020 577 421 425 2020Natur.577.421X 1:CAS:528:DC%2BB3cXlsleisA%3D%3D 31915379 7308074
M.B. Ryan et al. Vertical pathway inhibition overcomes adaptive feedback resistance to KrasG12C inhibition Clin. Cancer Res. 2020 26 1633 1643 1:CAS:528:DC%2BB3cXit1GnurjP 31776128
Ivanisevic, T. et al. Increased dosage of wild-type KRAS protein drives KRAS-mutant lung tumorigenesis and drug resistance. Preprint at bioRxivhttps://doi.org/10.1101/2024.02.27.582346 (2024).
C. Schulze et al. Chemical remodeling of a cellular chaperone to target the active state of mutant KRAS Science 2023 381 794 799 2023Sci..381.794S 1:CAS:528:DC%2BB3sXhslartL7I 37590355 10474815
Ambrogio et al. Modeling lung cancer evolution and pre-clinical response by orthotopic mouse allografts Cancer Res. 2014 74 5978 5988 1:CAS:528:DC%2BC2cXhvVGjtLbE 25217522
F. Lo Sardo et al. YAP/TAZ and EZH2 synergize to impair tumor suppressor activity of TGFBR2 in non-small cell lung cancer Cancer Lett. 2021 500 51 63 1:CAS:528:DC%2BB3cXis12htr3E 33296708
J.A. Hellyer S.K. Padda M. Diehn H.A. Wakelee Clinical implications of KEAP1-NFE2L2 mutations in NSCLC. J. Thorac. Oncol. 2021 16 395 403 1:CAS:528:DC%2BB3cXislSgs7zI 33307193
E. Cerami et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data Cancer Discov. 2012 2 401 404 22588877
J. Gao et al. 3D clusters of somatic mutations in cancer reveal numerous rare mutations as functional targets Genome Med. 2017 9 28115009 5260099
P. East et al. RAS oncogenic activity predicts response to chemotherapy and outcome in lung adenocarcinoma Nat. Commun. 2022 13 2022NatCo.13.5632E 1:CAS:528:DC%2BB38XisVyrsb7J 36163168 9512813
D. Kim et al. Pan-KRAS inhibitor disables oncogenic signalling and tumour growth Nature 2023 619 160 166 2023Natur.619.160K 1:CAS:528:DC%2BB3sXhtFaqtrzM 37258666 10322706
N. Tanaka et al. Clinical acquired resistance to krasg12c inhibition through a novel kras switch-ii pocket mutation and polyclonal alterations converging on ras–mapk reactivation Cancer Discov. 2021 11 1913 1922 1:CAS:528:DC%2BB3MXit1Sgsb3N 33824136 8338755
B.A. Lanman et al. Discovery of a covalent inhibitor of KRASG12C (AMG 510) for the treatment of solid tumors J. Med. Chem. 2020 63 52 65 1:CAS:528:DC%2BC1MXitlGitrrK 31820981
Y. Zhao et al. Diverse alterations associated with resistance to KRAS(G12C) inhibition Nature 2021 599 679 683 2021Natur.599.679Z 1:CAS:528:DC%2BB3MXisVOltLrJ 34759319 8887821
M. Salmón et al. Kras oncogene ablation prevents resistance in advanced lung adenocarcinoma J. Clin. Invest. 2023 133 e164413 36928090 10065067
Y. Tsai et al. Rapid idiosyncratic mechanisms of clinical resistance to KRAS G12C inhibition J. Clin. Invest. 2022 132 e155523 1:CAS:528:DC%2BB38Xmt1eisLo%3D 34990404 8843735
D. Kim J.Y. Xue P. Lito Targeting KRAS(G12C): from inhibitory mechanism to modulation of antitumor effects in patients Cell 2020 183 850 859 1:CAS:528:DC%2BB3cXitFSns7fI 33065029 7669705
Ambrogio, C. et al. KRAS dimerization impacts MEK inhibitor sensitivity and oncogenic activity of mutant KRAS. Cell172, 857–868 (2018).
M. Burgess et al. KRAS allelic imbalance enhances fitness and modulates MAP kinase dependence in cancer Cell 2017 168 1 13
Negrao, M. et al. Co-mutations and KRAS G12C inhibitor efficacy in advanced NSCLC. Cancer Discov. 13, 1556–1571 (2023).
Lito, P., Solomon, M., Li, L.-S., Hansen, R. & Rosen, N. Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism. Science351, 604–608 (2016).
R.C. Hillig et al. Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS–SOS1 interaction Proc. Natl Acad. Sci. USA 2019 116 2551 2560 2019PNAS.116.2551H 1:CAS:528:DC%2BC1MXivVajs7w%3D 30683722 6377443
J. Hallin et al. The KRAS G12C inhibitor, MRTX849, provides insight toward therapeutic susceptibility of KRAS mutant cancers in mouse models and patients Cancer Discov. 2019 10 54 71 31658955 6954325
M. Holderfield Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy Nature 2024 629 919 926 2024Natur.629.919H 1:CAS:528:DC%2BB2cXnslygur8%3D 38589574 11111408
Wasko, U. N. et al. Tumor-selective effects of active RAS inhibition in pancreatic ductal adenocarcinoma. Nature629, 927–936 (2024).
J. Jingjing et al. Translational and therapeutic evaluation of RAS-GTP inhibition by RMC-6236 in RAS-driven cancers Cancer Discov. 2024 14 994 1017
M. Cereda et al. Patients with genetically heterogeneous synchronous colorectal cancer carry rare damaging germline mutations in immune-related genes Nat. Commun. 2016 7 2016NatCo..712072C 1:CAS:528:DC%2BC28XhtFCrsL3M 27377421 4935966
E. Morandi et al. HaTSPiL: a modular pipeline for high throughput sequencing data analysis PLoS ONE 2019 14 e0222512 1:CAS:528:DC%2BC1MXit1WisbzL 31613890 6793853
K. Cibulskis et al. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples Nat. Biotechnol. 2013 31 213 219 1:CAS:528:DC%2BC3sXjsFCntbc%3D 23396013 3833702
C.T. Saunders et al. Strelka: accurate somatic small-variant calling from sequenced tumor-normal sample pairs Bioinformatics 2012 28 1811 1817 1:CAS:528:DC%2BC38XhtVSgtr%2FM 22581179
D.C. Koboldt et al. VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing Genome Res. 2012 22 568 576 1:CAS:528:DC%2BC38XjsV2ltr4%3D 22300766 3290792
F. Favero et al. Sequenza: allele-specific copy number and mutation profiles from tumor sequencing data Ann. Oncol. 2015 26 64 70 1:STN:280:DC%2BC2M3gvFOqtA%3D%3D 25319062
R. D’Aurizio et al. Enhanced copy number variants detection from whole-exome sequencing data using EXCAVATOR2 Nucleic Acids Res. 2016 44 e154 27507884 5175347
Frankish, A. et al. GENCODE reference annotation for the human and mouse genomes. Nucleic Acids Res.47, D766–D773 (2019).
K. Wang M. Li H. Hakonarson ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data Nucleic Acids Res. 2010 38 e164 20601685 2938201
D. Repana et al. The Network of Cancer Genes (NCG): a comprehensive catalogue of known and candidate cancer genes from cancer sequencing screens Genome Biol. 2019 20 30606230 6317252
Melloni, G. E. M. et al. Precision Trial Drawer, a Computational Tool to Assist Planning of Genomics-Driven Trials in Oncology. JCO Precis Oncol.2, 1–16 (2018).
Li, Q. et al. CancerVar: An artificial intelligence-empowered platform for clinical interpretation of somatic mutations in cancer. Sci. Adv.8, eabj1624 (2022).
Li, M. M. et al. Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. J. Mol. Diagn.19, 4–23 (2017).
A. Roth et al. PyClone: statistical inference of clonal population structure in cancer Nat. Methods 2014 11 396 398 1:CAS:528:DC%2BC2cXktlGntbg%3D 24633410 4864026
H.X. Dang et al. ClonEvol: clonal ordering and visualization in cancer sequencing Ann. Oncol. 2017 28 3076 3082 1:STN:280:DC%2BC1M%2FisFCisA%3D%3D 28950321 5834020
M. Del Giudice et al. FOXA1 regulates alternative splicing in prostate cancer Cell Rep. 2022 40 111404 36170835 9532847
Meng, P. et al. Detecting therapy-guiding RNA aberrations in platelets of non-small cell lung cancer patients. Preprint at medRxiv https://doi.org/10.1101/2021.01.26.21250013 (2021).
P.K.S. Ng et al. Systematic functional annotation of somatic mutations in cancer Cancer Cell 2018 33 450 462.e10 1:CAS:528:DC%2BC1cXksVent7o%3D 29533785 5926201
F.M. Siswanto A. Oguro S. Imaoka Sp1 is a substrate of Keap1 and regulates the activity of CRL4AWDR23 ubiquitin ligase toward Nrf2 J. Biol. Chem. 2021 296 100704 1:CAS:528:DC%2BB3MXhtFSku7vM 33895141 8141886
A. Ianevski A. Giri T. Aittokallio SynergyFinder 3.0: an interactive analysis and consensus interpretation of multi-drug synergies across multiple samples Nucleic Acids Res. 2022 50 739 743
B. Yadav K. Wennerberg T. Aittokallio J. Tang Searching for drug synergy in complex dose-response landscapes using an interaction potency model Comput. Struct. Biotechnol. J. 2015 13 504 513 1:CAS:528:DC%2BC28XhtFOlsbjK 26949479 4759128
G.Y. Di Veroli et al. Combenefit: an interactive platform for the analysis and visualization of drug combinations Bioinformatics 2016 32 2866 2868 27153664 5018366
