Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 May 11;11(1):65.
doi: 10.1186/s13045-018-0608-2.

BCL-2 as therapeutic target for hematological malignancies

Guilherme Fleury Perini  1 , Glaciano Nogueira Ribeiro  2 , Jorge Vaz Pinto Neto  3 , Laura Tojeiro Campos  4 , Nelson Hamerschlak  5
Affiliations
Review

BCL-2 as therapeutic target for hematological malignancies

Guilherme Fleury Perini et al. J Hematol Oncol. .

Abstract

Disruption of the physiologic balance between cell proliferation and cell death is an important step of cancer development. Increased resistance to apoptosis is a key oncogenic mechanism in several hematological malignancies and, in many cases, especially in lymphoid neoplasias, has been attributed to the upregulation of BCL-2. The BCL-2 protein is the founding member of the BCL-2 family of apoptosis regulators and was the first apoptosis modulator to be associated with cancer. The recognition of the important role played by BCL-2 for cancer development and resistance to treatment made it a relevant target for therapy for many diseases, including solid tumors and hematological neoplasias. Among the different strategies that have been developed to inhibit BCL-2, BH3-mimetics have emerged as a novel class of compounds with favorable results in different clinical settings, including chronic lymphocytic leukemia (CLL). In April 2016, the first inhibitor of BCL-2, venetoclax, was approved by the US Food and Drug Administration for the treatment of patients with CLL who have 17p deletion and had received at least one prior therapy. This review focuses on the relevance of BCL-2 for apoptosis modulation at the mitochondrial level, its potential as therapeutic target for hematological malignancies, and the results obtained with selective inhibitors belonging to the BH3-mimetics, especially venetoclax used in monotherapy or in combination with other agents.

Keywords: Apoptosis; BCL-2; BH3-mimetics; Hematological malignancies; Leukemia; Lymphoma; Resistance; Venetoclax.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Competing interests

GFP has served as consultant and as speaker to AbbVie, Janssen, and Takeda; has received sponsorship for scientific events from Abbvie, Janssen, Roche, and Takeda; and is Advisory Board member of Janssen.

GNR has served as consultant to Janssen; as speaker to Janssen, Roche, and AbbVie; as investigator to Janssen; has received sponsorship for scientific events from Janssen and AbbVie; and is Advisory Board member of Janssen.

JVPN has served as consultant to AbbVie, Celgene, Janssen, Roche, and Takeda; as speaker to Janssen, Roche, and Takeda; as investigator to Roche; has received sponsorship for scientific events from Celgene, Janssen, Roche, and Takeda; and is Advisory Board member of Celgene, Janssen, Roche, and Takeda.

LTC is employee of AbbVie Brazil.

NH has served as consultant and/or as speaker to Takeda, Roche, Novartis, Amgen, and United Medical; and is Advisory Board member of AbbVie.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

    1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–674. doi: 10.1016/j.cell.2011.02.013. - DOI - PubMed
    1. Delbridge AR, Grabow S, Strasser A, Vaux DL. Thirty years of BCL-2: translating cell death discoveries into novel cancer therapies. Nat Rev Cancer. 2016;16(2):99–109. doi: 10.1038/nrc.2015.17. - DOI - PubMed
    1. Hainaut P, Plymoth A. Targeting the hallmarks of cancer: towards a rational approach to next-generation cancer therapy. Curr Opin Oncol. 2013;25(1):50–51. doi: 10.1097/CCO.0b013e32835b651e. - DOI - PubMed
    1. Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002;2(9):647–656. doi: 10.1038/nrc883. - DOI - PubMed
    1. Tsujimoto Y, Gorham J, Cossman J, Jaffe E, Croce CM. The t(14;18) chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining. Science. 1985;229(4720):1390–1393. doi: 10.1126/science.3929382. - DOI - PubMed

Publication types

MeSH terms

Substances