enzastaurin; epidermal growth factor receptor; glioblastoma; glioma stem cells; neural stem cells; neuregulin; neurogenesis; protein kinase C; temozolomide; Medicine (miscellaneous); Biochemistry, Genetics and Molecular Biology (all)
Abstract :
[en] Glioblastoma (GBM) is the most frequent and aggressive primary brain tumor and is associated with a poor prognosis. Despite the use of combined treatment approaches, recurrence is almost inevitable and survival longer than 14 or 15 months after diagnosis is low. It is therefore necessary to identify new therapeutic targets to fight GBM progression and recurrence. Some publications have pointed out the role of glioma stem cells (GSCs) as the origin of GBM. These cells, with characteristics of neural stem cells (NSC) present in physiological neurogenic niches, have been proposed as being responsible for the high resistance of GBM to current treatments such as temozolomide (TMZ). The protein Kinase C (PKC) family members play an essential role in transducing signals related with cell cycle entrance, differentiation and apoptosis in NSC and participate in distinct signaling cascades that determine NSC and GSC dynamics. Thus, PKC could be a suitable druggable target to treat recurrent GBM. Clinical trials have tested the efficacy of PKCβ inhibitors, and preclinical studies have focused on other PKC isozymes. Here, we discuss the idea that other PKC isozymes may also be involved in GBM progression and that the development of a new generation of effective drugs should consider the balance between the activation of different PKC subtypes.
Geribaldi-Doldán, Noelia ✱; Departamento de Anatomía y Embriología Humanas, Facultad de Medicina, Universidad de Cádiz, 11003 Cádiz, Spain ; Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cádiz, Spain
Hervás-Corpión, Irati ✱; Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cádiz, Spain ; Unidad de Investigación, Hospital Universitario Puerta del Mar de Cádiz, 11009 Cádiz, Spain
Gómez Oliva, Ricardo ; Université de Liège - ULiège > GIGA > GIGA Neurosciences - Molecular Regulation of Neurogenesis ; Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cádiz, Spain ; Área de Fisiología, Facultad de Medicina, Universidad de Cádiz, 11003 Cádiz, Spain
Domínguez-García, Samuel; Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cádiz, Spain ; Área de Fisiología, Facultad de Medicina, Universidad de Cádiz, 11003 Cádiz, Spain
Ruiz, Félix A ; Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cádiz, Spain ; Unidad de Investigación, Hospital Universitario Puerta del Mar de Cádiz, 11009 Cádiz, Spain ; Área de Nutrición, Facultad de Medicina, Universidad de Cádiz, 11003 Cádiz, Spain
Iglesias-Lozano, Irene ; Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cádiz, Spain ; Unidad de Investigación, Hospital Universitario Puerta del Mar de Cádiz, 11009 Cádiz, Spain
Carrascal, Livia ; Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cádiz, Spain ; Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain
Pardillo-Díaz, Ricardo; Departamento de Anatomía y Embriología Humanas, Facultad de Medicina, Universidad de Cádiz, 11003 Cádiz, Spain ; Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cádiz, Spain
Gil-Salú, José L; Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cádiz, Spain ; Unidad de Investigación, Hospital Universitario Puerta del Mar de Cádiz, 11009 Cádiz, Spain
Nunez-Abades, Pedro ; Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cádiz, Spain ; Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain
Valor, Luis M ; Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cádiz, Spain ; Unidad de Investigación, Hospital Universitario Puerta del Mar de Cádiz, 11009 Cádiz, Spain ; Currently at Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), 03010 Alicante, Spain
Castro, Carmen; Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cádiz, Spain ; Área de Fisiología, Facultad de Medicina, Universidad de Cádiz, 11003 Cádiz, Spain
✱ These authors have contributed equally to this work.
Language :
English
Title :
Targeting Protein Kinase C in Glioblastoma Treatment.
ERDF - European Regional Development Fund Junta de Andalucía. Consejería de Salud y Familias EC - European Commission
Funding text :
Funding: This research was co-financed by the Integrated Territorial Investment Operational Programme of the European Commission and by the Department of Department of Health and Families (Consejería de Salud y Familias) of the Regional Government of Andalusia. Project reference: ITI-0042-2019: ITI Cadiz 2019. L.M.V. is the recipient of a Miguel Servet II contract (CPII20/00025) financed by the Instituto de Salud Carlos III and Fondo Social Europeo 2014-2020, Programa Estatal de Promoción del Talento y su empleabilidad en I + D + i.This research was co-financed by the Integrated Territorial Investment Operational Programme of the European Commission and by the Department of Department of Health and Families (Consejer?a de Salud y Familias) of the Regional Government of Andalusia. Project reference: ITI-0042-2019: ITI Cadiz 2019. L.M.V. is the recipient of a Miguel Servet II contract (CPII20/00025) financed by the Instituto de Salud Carlos III and Fondo Social Europeo 2014-2020, Programa Estatal de Promoci?n del Talento y su empleabilidad en I + D + i.
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