Bcl-2 (B-cell lymphoma-2gene) is a member of Bcl-2 family, which contains Bcl-2, Bcl-xi, Bax, Bak, Bid, and Bad. Bcl-2, localized mainly on the outer membrane of the mitochondrion, is a very important antiapoptosis factor, by preventing the release of cytochrome C and then restraining the activation of the caspase, which is crucial for cell apoptosis.

Bcl-2 is specifically considered an important anti-apoptotic protein and when this gene is overexpressed, unchecked cellular proliferation ensues.

Cancers that depend on Bcl-2 for survival are:

  • In follicular lymphoma, an estimated 90% of patients harbor at (14;18) chromosomal translocation in tumor cells, which affects the IgH locus on chromosome 14 and the Bcl-2 locus on chromosome 18 and cause overexpression of the Bcl-2 protein.
  • Although 95% of patients with chronic lymphocytic leukemia (CLL) have a relatively high level of BCL-2 expression, only less than 5% of patients CLL with harbor a detectable Bcl-2 gene rearrangement.
  • Diverse solid tumors such as a prostate, breast, and small cell and non-small cell lung cancers have been associated with Inappropriate expression of BCL-2.

Targeting the anti-apoptotic Bcl-2 family of proteins can improve apoptosis and thus overcome drug resistance to cancer chemotherapy and targeted and selective Bcl-2 inhibitors currently in the clinic include:

  • Oblimersen: Oblimersen sodium (G3139, Genasense) is a phosphorothioate BCL2 antisense oligodeoxynucleotide that targets BCL-2 mRNA.
  • ABT-737: ABT-737 (A-779024, Abbott Laboratories) is a small molecule that targets anti-apoptotic Bcl-2 family proteins (Bcl-2, Bcl-XL, and Bcl-w)
  • Navitoclax (ABT-263): ABT-263, an oral version of ABT-737, shares similar biological properties with ABT-737. ABT-263 is active as a single agent in small cell lung cancer xenografts, and it enhanced the activity of other chemotherapy agents in preclinical studies of B-cell lymphoma and multiple myeloma.
  • Venetoclax (ABT-199):  Venetoclax (VEN, ABT-199/GDC-0199) is an orally bioavailable BH3-mimetic that inhibits the anti-apoptotic B-cell lymphoma/leukemia 2 (BCL2) protein explicitly.


  • Kang MH, Reynolds CP. Bcl-2 Inhibitors: Targeting Mitochondrial Apoptotic Pathways in Cancer Therapy. Clinical cancer research : an official journal of the American Association for Cancer Research. 2009;15(4):1126-1132. doi:10.1158/1078-0432.CCR-08-0144. (link)
  • Itchaki G, Brown JR. The potential of venetoclax (ABT-199) in chronic lymphocytic leukemia. Therapeutic Advances in Hematology. 2016;7(5):270-287. doi:10.1177/2040620716655350. (link)
  • Bodur C, Basaga H. Bcl-2 inhibitors: emerging drugs in cancer therapy. Curr Med Chem. 2012;19(12):1804-20. (link)

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