Resistance to Targeted Therapies in Renal Cancer: The Importance of Changing the Mechanism of Action

Renal cell carcinoma (RCC) is a complex disease characterized by mutations in several genes. Loss of function of the von Hippel-Lindau (VHL) is a very common finding in RCC and leads to up-regulation of hypoxia-inducible factor (HIF)-responsive genes accountable for angiogenesis and cell growth, suc...

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Autores: Duran, I., Lambea, Julio, Maroto, P., González Larriba, José Luis, Flores, Luis, Granados Principal, S., Graupera i Garcia-Milà, Mariona, Sáez, B., Vivancos, A., Casanovas i Casanovas, Oriol
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2016
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/171618
Acceso en línea:https://hdl.handle.net/2445/171618
Access Level:acceso abierto
Palabra clave:Càncer de ronyó
Teràpia genètica
Renal cancer
Gene therapy
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spelling Resistance to Targeted Therapies in Renal Cancer: The Importance of Changing the Mechanism of ActionDuran, I.Lambea, JulioMaroto, P.González Larriba, José LuisFlores, LuisGranados Principal, S.Graupera i Garcia-Milà, MarionaSáez, B.Vivancos, A.Casanovas i Casanovas, OriolCàncer de ronyóTeràpia genèticaRenal cancerGene therapyRenal cell carcinoma (RCC) is a complex disease characterized by mutations in several genes. Loss of function of the von Hippel-Lindau (VHL) is a very common finding in RCC and leads to up-regulation of hypoxia-inducible factor (HIF)-responsive genes accountable for angiogenesis and cell growth, such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Binding of these proteins to tyrosine kinase receptors (TKR) on endothelial cells promotes angiogenesis. Promotion of angiogenesis is in part due to the activation of the phosphatidylinositol-3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) pathway. Inhibition of this pathway decreases protein translation and inhibits both angiogenesis and tumour cell proliferation. Although tyrosine kinase inhibitors (TKIs) stand as the main first-line treatment option for advanced RCC, eventually all patients will become resistant to TKIs. Resistance can be overcome by using second-line treatments with different mechanisms of action, such as inhibitors of mTOR, c-MET, programmed death 1 (PD-1) receptor, or the combination of an mTOR inhibitor (mTORi) with a TKI. In this article, we briefly review current evidence regarding mechanisms of resistance in RCC and treatment strategies to overcome resistance with a special focus on the PI3K/AKT/mTOR pathway.Springer Science and Business Media LLC2020202020162020info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion50 p.application/pdfhttps://hdl.handle.net/2445/171618Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1007/s11523-016-0463-4Targeted Oncology, 2016, vol. 12, issue. 1, p. 19-35https://doi.org/10.1007/s11523-016-0463-4(c) Springer Science and Business Media LLC, 2016info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1716182026-05-29T05:05:01Z
dc.title.none.fl_str_mv Resistance to Targeted Therapies in Renal Cancer: The Importance of Changing the Mechanism of Action
title Resistance to Targeted Therapies in Renal Cancer: The Importance of Changing the Mechanism of Action
spellingShingle Resistance to Targeted Therapies in Renal Cancer: The Importance of Changing the Mechanism of Action
Duran, I.
Càncer de ronyó
Teràpia genètica
Renal cancer
Gene therapy
title_short Resistance to Targeted Therapies in Renal Cancer: The Importance of Changing the Mechanism of Action
title_full Resistance to Targeted Therapies in Renal Cancer: The Importance of Changing the Mechanism of Action
title_fullStr Resistance to Targeted Therapies in Renal Cancer: The Importance of Changing the Mechanism of Action
title_full_unstemmed Resistance to Targeted Therapies in Renal Cancer: The Importance of Changing the Mechanism of Action
title_sort Resistance to Targeted Therapies in Renal Cancer: The Importance of Changing the Mechanism of Action
dc.creator.none.fl_str_mv Duran, I.
Lambea, Julio
Maroto, P.
González Larriba, José Luis
Flores, Luis
Granados Principal, S.
Graupera i Garcia-Milà, Mariona
Sáez, B.
Vivancos, A.
Casanovas i Casanovas, Oriol
author Duran, I.
author_facet Duran, I.
Lambea, Julio
Maroto, P.
González Larriba, José Luis
Flores, Luis
Granados Principal, S.
Graupera i Garcia-Milà, Mariona
Sáez, B.
Vivancos, A.
Casanovas i Casanovas, Oriol
author_role author
author2 Lambea, Julio
Maroto, P.
González Larriba, José Luis
Flores, Luis
Granados Principal, S.
Graupera i Garcia-Milà, Mariona
Sáez, B.
Vivancos, A.
Casanovas i Casanovas, Oriol
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer de ronyó
Teràpia genètica
Renal cancer
Gene therapy
topic Càncer de ronyó
Teràpia genètica
Renal cancer
Gene therapy
description Renal cell carcinoma (RCC) is a complex disease characterized by mutations in several genes. Loss of function of the von Hippel-Lindau (VHL) is a very common finding in RCC and leads to up-regulation of hypoxia-inducible factor (HIF)-responsive genes accountable for angiogenesis and cell growth, such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Binding of these proteins to tyrosine kinase receptors (TKR) on endothelial cells promotes angiogenesis. Promotion of angiogenesis is in part due to the activation of the phosphatidylinositol-3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) pathway. Inhibition of this pathway decreases protein translation and inhibits both angiogenesis and tumour cell proliferation. Although tyrosine kinase inhibitors (TKIs) stand as the main first-line treatment option for advanced RCC, eventually all patients will become resistant to TKIs. Resistance can be overcome by using second-line treatments with different mechanisms of action, such as inhibitors of mTOR, c-MET, programmed death 1 (PD-1) receptor, or the combination of an mTOR inhibitor (mTORi) with a TKI. In this article, we briefly review current evidence regarding mechanisms of resistance in RCC and treatment strategies to overcome resistance with a special focus on the PI3K/AKT/mTOR pathway.
publishDate 2016
dc.date.none.fl_str_mv 2016
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/171618
url https://hdl.handle.net/2445/171618
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1007/s11523-016-0463-4
Targeted Oncology, 2016, vol. 12, issue. 1, p. 19-35
https://doi.org/10.1007/s11523-016-0463-4
dc.rights.none.fl_str_mv (c) Springer Science and Business Media LLC, 2016
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Springer Science and Business Media LLC, 2016
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 50 p.
application/pdf
dc.publisher.none.fl_str_mv Springer Science and Business Media LLC
publisher.none.fl_str_mv Springer Science and Business Media LLC
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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