Please use this identifier to cite or link to this item: https://doi.org/10.3390/cancers12030574
Title: Targeting mitochondrial apoptosis to overcome treatment resistance in cancer
Authors: Ngoi N.Y.L.
Choong C.
Lee J.
Bellot G. 
Wong A.L.A. 
Goh B.C. 
Pervaiz S. 
Keywords: BCL-2
BCL-xL
MCL-1
apoptosis
cancer therapeutics
targeted therapy
Issue Date: 1-Mar-2020
Publisher: MDPI AG
Citation: Ngoi N.Y.L., Choong C., Lee J., Bellot G., Wong A.L.A., Goh B.C., Pervaiz S. (2020-03-01). Targeting mitochondrial apoptosis to overcome treatment resistance in cancer. Cancers 12 (3) : 574-574. ScholarBank@NUS Repository. https://doi.org/10.3390/cancers12030574
Abstract: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. Deregulated cellular apoptosis is a hallmark of cancer and chemotherapy resistance. The B-cell lymphoma 2 (BCL-2) protein family members are sentinel molecules that regulate the mitochondrial apoptosis machinery and arbitrate cell fate through a delicate balance between pro-and anti-apoptotic factors. The recognition of the anti-apoptotic BCL2 gene as an oncogenic driver in hematological malignancies has directed attention toward unraveling the biological significance of each of the BCL-2 superfamily members in cancer progression and garnered interest in the targeting of apoptosis in cancer therapy. Accordingly, the approval of venetoclax (ABT-199), a small molecule BCL-2 inhibitor, in patients with chronic lymphocytic leukemia and acute myeloid leukemia has become the proverbial torchbearer for novel candidate drug approaches selectively targeting the BCL-2 superfamily. Despite the inspiring advances in this field, much remains to be learned regarding the optimal therapeutic context for BCL-2 targeting. Functional assays, such as through BH3 profiling, may facilitate prediction of treatment response, development of drug resistance and shed light on rational combinations of BCL-2 inhibitors with other branches of cancer therapy. This review summarizes the pathological roles of the BCL-2 family members in cancer, discusses the current landscape of their targeting in clinical practice, and highlights the potential for future therapeutic inroads in this important area.
Source Title: Cancers
URI: https://scholarbank.nus.edu.sg/handle/10635/169447
ISSN: 20726694
DOI: 10.3390/cancers12030574
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