Cancers, Vol. 12, Pages 574: Targeting Mitochondrial Apoptosis to Overcome Treatment Resistance in Cancer

Cancers, Vol. 12, Pages 574: Targeting Mitochondrial Apoptosis to Overcome Treatment Resistance in Cancer Cancers doi: 10.3390/cancers12030574 Authors: Natalie Yan Li Ngoi Clarice Choong Joanne Lee Gregory Bellot Andrea Li Ann Wong Boon Cher Goh Shazib Pervaiz 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 oth...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research