BCL2 Family Inhibitors in the Biology and Treatment of Multiple Myeloma

Vikas A Gupta,1 James Ackley,2 Jonathan L Kaufman,1 Lawrence H Boise1 1Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Emory University School of Medicine, Atlanta, GA, USA; 2Cancer Biology Graduate Program, Winship Cancer Institute of Emory University, E...

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Autores principales:	Gupta VA, Ackley J, Kaufman JL, Boise LH
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	multiple myeloma bcl2 family inhibitors venetoclax Diseases of the blood and blood-forming organs RC633-647.5
Acceso en línea:	https://doaj.org/article/e6d2cffa79a14fa8a38bd9e29bf1c781
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spelling	oai:doaj.org-article:e6d2cffa79a14fa8a38bd9e29bf1c7812021-12-02T13:16:23ZBCL2 Family Inhibitors in the Biology and Treatment of Multiple Myeloma1179-9889https://doaj.org/article/e6d2cffa79a14fa8a38bd9e29bf1c7812021-03-01T00:00:00Zhttps://www.dovepress.com/bcl2-family-inhibitors-in-the-biology-and-treatment-of-multiple-myelom-peer-reviewed-article-BLCTThttps://doaj.org/toc/1179-9889Vikas A Gupta,1 James Ackley,2 Jonathan L Kaufman,1 Lawrence H Boise1 1Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Emory University School of Medicine, Atlanta, GA, USA; 2Cancer Biology Graduate Program, Winship Cancer Institute of Emory University, Emory University School of Medicine, Atlanta, GA, USACorrespondence: Lawrence H BoiseDepartment of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Emory University School of Medicine, 1365 Clifton Road NE, Rm C4078, Atlanta, GA, 30322, USATel +1 404-778-4724Fax +1 404-778-5530Email lboise@emory.eduVikas A GuptaDepartment of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Emory University School of Medicine, 1365 Clifton Road NE, Rm C4090, Atlanta, GA, 30322, USATel +1 404-778-6485Fax +1 404-778-3260Email vikas.gupta@emory.eduAbstract: Although much progress has been made in the treatment of multiple myeloma, the majority of patients fail to be cured and require numerous lines of therapy. Inhibitors of the BCL2 family represent an exciting new class of drugs with a novel mechanism of action that are likely to have activity as single agents and in combination with existing myeloma therapies. The BCL2 proteins are oncogenes that promote cell survival and are frequently upregulated in multiple myeloma, making them attractive targets. Venetoclax, a BCL2 specific inhibitor, is furthest along in development and has shown promising results in a subset of myeloma characterized by the t(11;14) translocation. Combining venetoclax with proteasome inhibitors and monoclonal antibodies has improved responses in a broader group of patients, but has come at the expense of a toxicity safety signal that requires additional follow-up. MCL1 inhibitors are likely to be effective in a broader range of patients and are currently in early clinical trials. This review will cover much of what is known about the biology of these drugs, biomarkers that predict response, mechanisms of resistance, and unanswered questions as they pertain to multiple myeloma.Keywords: multiple myeloma, BCL2 family inhibitors, venetoclaxGupta VAAckley JKaufman JLBoise LHDove Medical Pressarticlemultiple myelomabcl2 family inhibitorsvenetoclaxDiseases of the blood and blood-forming organsRC633-647.5ENBlood and Lymphatic Cancer: Targets and Therapy, Vol Volume 11, Pp 11-24 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	multiple myeloma bcl2 family inhibitors venetoclax Diseases of the blood and blood-forming organs RC633-647.5
spellingShingle	multiple myeloma bcl2 family inhibitors venetoclax Diseases of the blood and blood-forming organs RC633-647.5 Gupta VA Ackley J Kaufman JL Boise LH BCL2 Family Inhibitors in the Biology and Treatment of Multiple Myeloma
description	Vikas A Gupta,1 James Ackley,2 Jonathan L Kaufman,1 Lawrence H Boise1 1Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Emory University School of Medicine, Atlanta, GA, USA; 2Cancer Biology Graduate Program, Winship Cancer Institute of Emory University, Emory University School of Medicine, Atlanta, GA, USACorrespondence: Lawrence H BoiseDepartment of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Emory University School of Medicine, 1365 Clifton Road NE, Rm C4078, Atlanta, GA, 30322, USATel +1 404-778-4724Fax +1 404-778-5530Email lboise@emory.eduVikas A GuptaDepartment of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Emory University School of Medicine, 1365 Clifton Road NE, Rm C4090, Atlanta, GA, 30322, USATel +1 404-778-6485Fax +1 404-778-3260Email vikas.gupta@emory.eduAbstract: Although much progress has been made in the treatment of multiple myeloma, the majority of patients fail to be cured and require numerous lines of therapy. Inhibitors of the BCL2 family represent an exciting new class of drugs with a novel mechanism of action that are likely to have activity as single agents and in combination with existing myeloma therapies. The BCL2 proteins are oncogenes that promote cell survival and are frequently upregulated in multiple myeloma, making them attractive targets. Venetoclax, a BCL2 specific inhibitor, is furthest along in development and has shown promising results in a subset of myeloma characterized by the t(11;14) translocation. Combining venetoclax with proteasome inhibitors and monoclonal antibodies has improved responses in a broader group of patients, but has come at the expense of a toxicity safety signal that requires additional follow-up. MCL1 inhibitors are likely to be effective in a broader range of patients and are currently in early clinical trials. This review will cover much of what is known about the biology of these drugs, biomarkers that predict response, mechanisms of resistance, and unanswered questions as they pertain to multiple myeloma.Keywords: multiple myeloma, BCL2 family inhibitors, venetoclax
format	article
author	Gupta VA Ackley J Kaufman JL Boise LH
author_facet	Gupta VA Ackley J Kaufman JL Boise LH
author_sort	Gupta VA
title	BCL2 Family Inhibitors in the Biology and Treatment of Multiple Myeloma
title_short	BCL2 Family Inhibitors in the Biology and Treatment of Multiple Myeloma
title_full	BCL2 Family Inhibitors in the Biology and Treatment of Multiple Myeloma
title_fullStr	BCL2 Family Inhibitors in the Biology and Treatment of Multiple Myeloma
title_full_unstemmed	BCL2 Family Inhibitors in the Biology and Treatment of Multiple Myeloma
title_sort	bcl2 family inhibitors in the biology and treatment of multiple myeloma
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/e6d2cffa79a14fa8a38bd9e29bf1c781
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BCL2 Family Inhibitors in the Biology and Treatment of Multiple Myeloma

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