Therapeutic targeting of Bcl-2 family for treatment of B-cell malignancies.
The BCL2 gene was discovered nearly 30 years ago, launching a field of scientific inquiry and medical research with the potential for delivering transformational therapeutics. Revealed by its involvement in chromosomal translocations of B-cell lymphomas, BCL2 is the founding member of a family of cell survival genes that endow cells with long life spans and provide protection from a myriad of cellular stresses, including chemotherapy. Anti-apoptotic Bcl-2 family members are commonly overexpressed in a variety of human malignancies through a diversity of genetic and epigenetic mechanisms. Here, we review therapeutic strategies for targeting Bcl-2 family members with an emphasis on B-cell malignancies, providing insights into their current promise and remaining challenges.
Early Discovery Biochemistry Department, Genentech, South San Francisco, CA, USA.
Jane
J
Huang
Wayne
W
Fairbrother
John C
JC
Reed
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015448:Leukemia, B-Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008958:Models, Molecular; D058990:Molecular Targeted Therapy / Q000379:methods*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2
Bcl-2; apoptosis; chemoresistance; leukemia; lymphoma