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REVIEW article

Front. Oncol.
Sec. Hematologic Malignancies
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1501950
This article is part of the Research Topic BCL-2 Family Inhibitors in Hematologic Malignancies View all 4 articles

BCL-2 inhibitors in hematological malignancies: biomarkers that predict response and management strategies

Provisionally accepted
Mariam Markouli Mariam Markouli 1*Maria Pagoni Maria Pagoni 2Panagiotis Diamantopoulos Panagiotis Diamantopoulos 3
  • 1 Chobanian & Avedisian School of Medicine, Boston University, Boston, Massachusetts, United States
  • 2 Evaggelismos General Hospital, Athens, Greece
  • 3 Laiko General Hospital of Athens, Athens, Greece

The final, formatted version of the article will be published soon.

    Apoptosis is an essential characteristic of cancer and its dysregular promotes tumor growth, clonal evolution, and treatment resistance. B-cell lymphoma-2 (BCL-2) protein family members are key to the intrinsic, mitochondrial apoptotic pathway. The inhibition of the BCL-2 family pro-survival proteins, which are frequently overexpressed in B-cell malignancies and pose a fundamental carcinogenic mechanism has been proposed as a promising therapeutic option, with venetoclax (ABT-199) being the first FDA-approved BCL-2 inhibitor. Unfortunately, although BCL-2 inhibition has shown remarkable results in a range of B-cell lymphoid cancers as well as AML, the development of resistance significantly reduces response rates in specific tumor subtypes. In this article, we explain the role of BCL-2 family proteins in apoptosis and their mechanism of action that justifies their inhibition as a potential treatment target in B-cell malignancies, including chronic lymphocytic leukemia, multiple myeloma, B-cell lymphomas, but also AML. We further analyze the tumor characteristics that result in the development of intrinsic or inherited resistance to BCL-2 inhibitors. Finally, we focus on the biomarkers that can be used to predict responses to treatment in the name of personalized medicine, with the goal of exploring alternative strategies to overcome resistance

    Keywords: English (United States) Font: 10 pt, Italic, Complex Script Font: pt, Italic Font: 10 pt, Complex Script Font: 10 pt, Italic Font: Italic, Complex Script Font: Italic Formatted: Font: (Default) +Headings CS (Times New Roman), Font color: Black

    Received: 25 Sep 2024; Accepted: 30 Dec 2024.

    Copyright: © 2024 Markouli, Pagoni and Diamantopoulos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Mariam Markouli, Chobanian & Avedisian School of Medicine, Boston University, Boston, 02118, Massachusetts, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.