The interactions between the members of the BH3 domain family of proteins play an important role in the development, progression, and prognosis in various subtypes of B-cell lymphomas. Therapies that selectively favor a pro-apoptotic environment are attractive strategies to overcome chemotherapy resistance in B-cell lymphomas. We previously reported that by targeting Bcl-2 family proteins with either Bcl-2 anti-sense oligonucleotides or GX15-070, a novel pan-inhibitor of the Bcl-2 family members, improved rituximab and/or chemotherapy activity in vitro and/or in vivo (
induces the expression of BH3 single domain proteins Puma and Noxa;
results in cell death and antiproliferation not only in RSCL and RRCL, but also from “treatment-refractory” primary DLBCL patient samples.
Our findings strongly suggest that GX15-070 added to bortezomib may result in a novel and potent therapeutic strategy against aggressive B-cell lymphomas.
Disclosure:Research Funding: USPHS grant PO1-CA103985 from the National Cancer Institute; 2007 American Society of Hematology Trainee Research Award.