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BCL-2 as therapeutic target for hematological malignancies
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946445/ https://www.ncbi.nlm.nih.gov/pubmed/29747654 http://dx.doi.org/10.1186/s13045-018-0608-2 |
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author | Perini, Guilherme Fleury Ribeiro, Glaciano Nogueira Pinto Neto, Jorge Vaz Campos, Laura Tojeiro Hamerschlak, Nelson |
author_facet | Perini, Guilherme Fleury Ribeiro, Glaciano Nogueira Pinto Neto, Jorge Vaz Campos, Laura Tojeiro Hamerschlak, Nelson |
author_sort | Perini, Guilherme Fleury |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5946445 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-59464452018-05-14 BCL-2 as therapeutic target for hematological malignancies Perini, Guilherme Fleury Ribeiro, Glaciano Nogueira Pinto Neto, Jorge Vaz Campos, Laura Tojeiro Hamerschlak, Nelson J Hematol Oncol Review 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. BioMed Central 2018-05-11 /pmc/articles/PMC5946445/ /pubmed/29747654 http://dx.doi.org/10.1186/s13045-018-0608-2 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Review Perini, Guilherme Fleury Ribeiro, Glaciano Nogueira Pinto Neto, Jorge Vaz Campos, Laura Tojeiro Hamerschlak, Nelson BCL-2 as therapeutic target for hematological malignancies |
title | BCL-2 as therapeutic target for hematological malignancies |
title_full | BCL-2 as therapeutic target for hematological malignancies |
title_fullStr | BCL-2 as therapeutic target for hematological malignancies |
title_full_unstemmed | BCL-2 as therapeutic target for hematological malignancies |
title_short | BCL-2 as therapeutic target for hematological malignancies |
title_sort | bcl-2 as therapeutic target for hematological malignancies |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946445/ https://www.ncbi.nlm.nih.gov/pubmed/29747654 http://dx.doi.org/10.1186/s13045-018-0608-2 |
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