Research in the Haffty laboratory at Rutgers Cancer Institute of New Jersey focuses on translational investigation of radiation therapies in combination with novel drugs targeting breast cancer and other cancers. The research involves molecular and cellular radiation biology from in vitro human cancer tissues to in vivo animal models.
Dr. Haffty's laboratory group has worked on targeting BCL-2 survival family members to enhance radiation's therapeutic effect in breast cancer cells. ABT-737, a small molecule inhibitor of BCL-2, was applied in targeting anti-apoptotic BCL-2 family proteins. Treatment with ABT-737 resulted in elevated MCL-1 levels in breast cancer cell lines. The Haffty group revealed that radiation diminished MCL-1 elevation induced by ABT-737; in addition, radiation down-regulated MCL-1 by promoting its degradation. Although radiation and ABT-737 exert a synergistic effect on breast cancer cell lines, ABT-737/ABT-263 induced thrombocytopenia which has implications for further clinical development. Other promising BCL-2 inhibitors, such as ABT 199 and ONC201, are tested in the Haffty laboratory to reveal agents that are enhanced by radiation and have the potential to deliver targeted therapy in the clinical setting.