Pharmacology and clinical potential of oblimersen sodium in the treatment of chronic lymphocytic leukemia

Abstract

Gautam Borthakur, Susan O'BrienDepartment of Leukemia, MD Anderson Cancer Center, Houston, TX, USAAbstract: Targeted inhibition of the Bcl-2 family of antiapoptotic proteins is expected to improve outcomes in chronic lymphocytic leukemia. Antisense oligonucleotides and small molecule inhibitors (BH3 mimetics) are two approaches that have been used to target Bcl-2 proteins. In this review, we summarize the experience with oblimersen sodium, an 18-base oligonucleotide targeting the first six codons of Bcl-2 mRNA, with particular focus on chronic lymphocytic leukemia. Despite evidence of improved outcomes in randomized trials of combination with chemoimmunotherapy, further development of this antisense approach has been slow, likely because of the clinical development of small molecule inhibitors.Keywords: oblimersen, Bcl-2, antisense, chronic lymphocytic leukemia