Targeting BCL2 in Chronic Lymphocytic Leukemia and Other Hematologic Malignancies.

Abstract

Apoptosis, the process of programmed cell death, occurs normally during development and aging. Members of the B-cell lymphoma 2 (BCL2) family of proteins are central regulators of apoptosis, and resistance to apoptosis is one of the hallmarks of cancer. Targeting the apoptotic pathway via BCL2 inhibitors has been considered a promising treatment strategy in the past decade. Initial efforts with small molecule BH3 mimetics such as ABT-737 and ABT-263 (navitoclax) pioneered the development of the first-in-class Food and Drug Administration (FDA)-approved oral BCL2 inhibitor, venetoclax. Venetoclax was approved for the treatment of chronic lymphocytic leukemia and acute myeloid leukemia, and is now being studied in a number of hematologic malignancies. Several other inhibitors targeting different BCL2 family members are now in early stages of development.

• Authors: Fevzi F Yalniz, William G Wierda
• Journal: Drugs (Drugs) Vol. 79 Issue 12 Pg. 1287-1304 (Aug 2019) ISSN: 1179-1950 [Electronic] New Zealand
• PMID: 31313099 (Publication Type: Journal Article, Review)

Chemical References

• ABT-737
• Aniline Compounds
• Antineoplastic Agents
• BCL2 protein, human
• Biphenyl Compounds
• Bridged Bicyclo Compounds, Heterocyclic
• Nitrophenols
• Piperazines
• Proto-Oncogene Proteins c-bcl-2
• Sulfonamides
• venetoclax
• navitoclax

Topics

• Aniline Compounds (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Apoptosis (drug effects)
• Biphenyl Compounds (therapeutic use)
• Bridged Bicyclo Compounds, Heterocyclic (therapeutic use)
• Drug Approval
• Hematologic Neoplasms (drug therapy)
• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell (drug therapy)
• Molecular Targeted Therapy
• Nitrophenols (therapeutic use)
• Piperazines (therapeutic use)
• Proto-Oncogene Proteins c-bcl-2 (antagonists & inhibitors, metabolism)
• Sulfonamides (therapeutic use)
• United States
• United States Food and Drug Administration