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      The role of BCL-2 family proteins in regulating apoptosis and cancer therapy

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          Abstract

          Apoptosis, as a very important biological process, is a response to developmental cues or cellular stress. Impaired apoptosis plays a central role in the development of cancer and also reduces the efficacy of traditional cytotoxic therapies. Members of the B-cell lymphoma 2 (BCL-2) protein family have pro- or anti-apoptotic activities and have been studied intensively over the past decade for their importance in regulating apoptosis, tumorigenesis, and cellular responses to anticancer therapy. Since the inflammatory response induced by apoptosis-induced cell death is very small, at present, the development of anticancer drugs targeting apoptosis has attracted more and more attention. Consequently, the focus of this review is to summarize the current research on the role of BCL-2 family proteins in regulating apoptosis and the development of drugs targeting BCL-2 anti-apoptotic proteins. Additionally, the mechanism of BCL-2 family proteins in regulating apoptosis was also explored. All the findings indicate the potential of BCL-2 family proteins in the therapy of cancer.

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          Most cited references165

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          Signatures of mutational processes in human cancer

          All cancers are caused by somatic mutations. However, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here, we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, kataegis, is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer with potential implications for understanding of cancer etiology, prevention and therapy.
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            Targeting apoptosis in cancer therapy

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              Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins

              The loss of vital cells within healthy tissues contributes to the development, progression and treatment outcomes of many human disorders, including neurological and infectious diseases as well as environmental and medical toxicities. Conversely, the abnormal survival and accumulation of damaged or superfluous cells drive prominent human pathologies such as cancers and autoimmune diseases. Apoptosis is an evolutionarily conserved cell death pathway that is responsible for the programmed culling of cells during normal eukaryotic development and maintenance of organismal homeostasis. This pathway is controlled by the BCL-2 family of proteins, which contains both pro-apoptotic and pro-survival members that balance the decision between cellular life and death. Recent insights into the dynamic interactions between BCL-2 family proteins and how they control apoptotic cell death in healthy and diseased cells have uncovered novel opportunities for therapeutic intervention. Importantly, the development of both positive and negative small-molecule modulators of apoptosis is now enabling researchers to translate the discoveries that have been made in the laboratory into clinical practice to positively impact human health.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                12 October 2022
                2022
                : 12
                : 985363
                Affiliations
                [1] 1School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine , Hefei, China
                [2] 2Gastrointestinal Surgery, Anhui Provincial Hospital , Hefei, China
                [3] 3School of Medical Informatics Engineering, Anhui University of Chinese Medicine , Hefei, China
                Author notes

                Edited by: Gavin P. McStay, Liverpool John Moores University, United Kingdom

                Reviewed by: Jiann-Ruey Hong, National Cheng Kung University, Taiwan; Dharmendra Kumar Yadav, Gachon University, South Korea; Manzar Alam, University of Texas Southwestern Medical Center, United States

                *Correspondence: Yinfeng Yang, yinfengyang@ 123456yeah.net ; Jinghui Wang, jhwang_dlut@ 123456163.com

                This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2022.985363
                9597512
                36313628
                d3ab80e3-baea-4388-b796-0b379c95dd77
                Copyright © 2022 Qian, Wei, Yang, Huang, Yang and Wang

                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) and the copyright owner(s) 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.

                History
                : 03 July 2022
                : 22 September 2022
                Page count
                Figures: 4, Tables: 2, Equations: 0, References: 167, Pages: 16, Words: 7451
                Categories
                Oncology
                Review

                Oncology & Radiotherapy
                bcl-2,apoptosis,cancer,autoimmunity,systematic
                Oncology & Radiotherapy
                bcl-2, apoptosis, cancer, autoimmunity, systematic

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