Targeting Mitochondrial Apoptosis to Overcome Treatment Resistance in Cancer

Cancers
Natalie Yan Li NgoiShazib Pervaiz

Abstract

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 therap...Continue Reading

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Citations

Mar 19, 2020·Cancers·Nicholas R JetteSusan P Lees-Miller
Apr 18, 2021·Nature Communications·Hudie WeiYongheng Chen
Apr 23, 2021·Journal of Hematology & Oncology·Haolan WangYongheng Chen
Jun 26, 2021·The International Journal of Biochemistry & Cell Biology·Yeliz AkaOzgur Kutuk
Jul 25, 2021·International Journal of Molecular Sciences·Daniel CacicTor Hervig
Sep 25, 2021·Clinical Anatomy : Official Journal of the American Association of Clinical Anatomists & the British Association of Clinical Anatomists·Nour S Erekat
Nov 9, 2021·Biochemical Society Transactions·João Pessoa

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Datasets Mentioned

BETA
ABT-737

Methods Mentioned

BETA
ubiquitination
GTPase
xenograft
xenografts

Clinical Trials Mentioned

NCT02427451
NCT02899052
NCT03584009
NCT03900884

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