The BCL2 Family: Key Mediators of the Apoptotic Response to Targeted Anticancer Therapeutics

The ability of cancer cells to suppress apoptosis is critical for carcinogenesis. The BCL2 family proteins comprise the sentinel network that regulates the mitochondrial or intrinsic apoptotic response. Recent advances in our understanding of apoptotic signaling pathways have enabled methods to iden...

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Bibliographic Details
Published in:Cancer discovery 2015-05, Vol.5 (5), p.475-487
Main Authors: Hata, Aaron N, Engelman, Jeffrey A, Faber, Anthony C
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Apoptosis - drug effects
Apoptosis - genetics
Apoptosis Regulatory Proteins - metabolism
Bcl-2-Like Protein 11
Biomarkers
Humans
Membrane Proteins - metabolism
Molecular Targeted Therapy
Neoplasms - genetics
Neoplasms - metabolism
Neoplasms - therapy
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-bcl-2 - genetics
Proto-Oncogene Proteins c-bcl-2 - metabolism
Signal Transduction - drug effects
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Summary:The ability of cancer cells to suppress apoptosis is critical for carcinogenesis. The BCL2 family proteins comprise the sentinel network that regulates the mitochondrial or intrinsic apoptotic response. Recent advances in our understanding of apoptotic signaling pathways have enabled methods to identify cancers that are "primed" to undergo apoptosis, and have revealed potential biomarkers that may predict which cancers will undergo apoptosis in response to specific therapies. Complementary efforts have focused on developing novel drugs that directly target antiapoptotic BCL2 family proteins. In this review, we summarize the current knowledge of the role of BCL2 family members in cancer development and response to therapy, focusing on targeted therapeutics, recent progress in the development of apoptotic biomarkers, and therapeutic strategies designed to overcome deficiencies in apoptosis. Apoptosis, long known to be important for response to conventional cytotoxic chemotherapy, has more recently been shown to be essential for the efficacy of targeted therapies. Approaches that increase the likelihood of a cancer to undergo apoptosis following therapy may help improve targeted treatment strategies. Cancer Discov; 5(5); 475-87. ©2015 AACR.
ISSN:2159-8274
2159-8290
DOI:10.1158/2159-8290.cd-15-0011