Venetoclax in Acute Myeloid Leukemia: Molecular Basis, Evidences for Preclinical and Clinical Efficacy and Strategies to Target Resistance

Venetoclax is a BH3-mimetics agent specifically interacting with the antiapoptotic protein BCL-2, facilitating cytochrome c release from mitochondria, subsequent caspases activation, and cell death. Utilization of venetoclax has profoundly changed the landscape of treatment for the poor-prognosis ca...

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Autores principales:	Sylvain Garciaz, Colombe Saillard, Yosr Hicheri, Marie-Anne Hospital, Norbert Vey
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	venetoclax BH3-mimetics acute myeloid leukemia apoptosis mitochondria Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/13c9af70caee4eefa21c165c9317d8d6
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spelling	oai:doaj.org-article:13c9af70caee4eefa21c165c9317d8d62021-11-25T17:01:28ZVenetoclax in Acute Myeloid Leukemia: Molecular Basis, Evidences for Preclinical and Clinical Efficacy and Strategies to Target Resistance10.3390/cancers132256082072-6694https://doaj.org/article/13c9af70caee4eefa21c165c9317d8d62021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5608https://doaj.org/toc/2072-6694Venetoclax is a BH3-mimetics agent specifically interacting with the antiapoptotic protein BCL-2, facilitating cytochrome c release from mitochondria, subsequent caspases activation, and cell death. Utilization of venetoclax has profoundly changed the landscape of treatment for the poor-prognosis category of AML patients unfit for intensive chemotherapy. In the phase III VIALE-A study, Venetoclax, in combination with the hypomethylating agent azacitidine, showed a 65% overall response rate and 14.7-month overall survival, in comparison with 22% and 8 months in the control arm. These results led to the widespread use of venetoclax in this indication. Other combination regimens, consisting of low-intensity, intensive, or targeted therapies are currently under evaluation. Despite promising results, preventing relapses or resistance to venetoclax is still an unmet clinical need. Numerous studies have been conducted to identify and overcome venetoclax resistance in preclinical models or in clinical trials, including the inhibition of other antiapoptotic proteins, the induction of proapoptotic BH3-only proteins, and/or the targeting of the mitochondrial metabolism and machinery.Sylvain GarciazColombe SaillardYosr HicheriMarie-Anne HospitalNorbert VeyMDPI AGarticlevenetoclaxBH3-mimeticsacute myeloid leukemiaapoptosismitochondriaNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5608, p 5608 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	venetoclax BH3-mimetics acute myeloid leukemia apoptosis mitochondria Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	venetoclax BH3-mimetics acute myeloid leukemia apoptosis mitochondria Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Sylvain Garciaz Colombe Saillard Yosr Hicheri Marie-Anne Hospital Norbert Vey Venetoclax in Acute Myeloid Leukemia: Molecular Basis, Evidences for Preclinical and Clinical Efficacy and Strategies to Target Resistance
description	Venetoclax is a BH3-mimetics agent specifically interacting with the antiapoptotic protein BCL-2, facilitating cytochrome c release from mitochondria, subsequent caspases activation, and cell death. Utilization of venetoclax has profoundly changed the landscape of treatment for the poor-prognosis category of AML patients unfit for intensive chemotherapy. In the phase III VIALE-A study, Venetoclax, in combination with the hypomethylating agent azacitidine, showed a 65% overall response rate and 14.7-month overall survival, in comparison with 22% and 8 months in the control arm. These results led to the widespread use of venetoclax in this indication. Other combination regimens, consisting of low-intensity, intensive, or targeted therapies are currently under evaluation. Despite promising results, preventing relapses or resistance to venetoclax is still an unmet clinical need. Numerous studies have been conducted to identify and overcome venetoclax resistance in preclinical models or in clinical trials, including the inhibition of other antiapoptotic proteins, the induction of proapoptotic BH3-only proteins, and/or the targeting of the mitochondrial metabolism and machinery.
format	article
author	Sylvain Garciaz Colombe Saillard Yosr Hicheri Marie-Anne Hospital Norbert Vey
author_facet	Sylvain Garciaz Colombe Saillard Yosr Hicheri Marie-Anne Hospital Norbert Vey
author_sort	Sylvain Garciaz
title	Venetoclax in Acute Myeloid Leukemia: Molecular Basis, Evidences for Preclinical and Clinical Efficacy and Strategies to Target Resistance
title_short	Venetoclax in Acute Myeloid Leukemia: Molecular Basis, Evidences for Preclinical and Clinical Efficacy and Strategies to Target Resistance
title_full	Venetoclax in Acute Myeloid Leukemia: Molecular Basis, Evidences for Preclinical and Clinical Efficacy and Strategies to Target Resistance
title_fullStr	Venetoclax in Acute Myeloid Leukemia: Molecular Basis, Evidences for Preclinical and Clinical Efficacy and Strategies to Target Resistance
title_full_unstemmed	Venetoclax in Acute Myeloid Leukemia: Molecular Basis, Evidences for Preclinical and Clinical Efficacy and Strategies to Target Resistance
title_sort	venetoclax in acute myeloid leukemia: molecular basis, evidences for preclinical and clinical efficacy and strategies to target resistance
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/13c9af70caee4eefa21c165c9317d8d6
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Venetoclax in Acute Myeloid Leukemia: Molecular Basis, Evidences for Preclinical and Clinical Efficacy and Strategies to Target Resistance

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