Newly Devised Compound Promotes Cancer Cell Destruction

The BCL-2 (B-cell lymphoma 2) protein family plays a key role in determining whether cancer cells survive in response to therapy or undergo apoptosis. Scientists have recently developed a compound modeled from the proapoptotic, the death domain of BCL-2, the BIM BH3 domain.

Cells are pushed toward apoptosis by expression of pro-apoptotic BCL-2 proteins. However, cancer cells respond to therapy by increasing expression of antiapoptotic proteins, which bind and neutralize proapoptotic family members and mediate therapeutic resistance. Therefore, development of therapeutic approaches to offset resistance to apoptosis will be vital to clinical developments toward cancer therapy.

A research group from the Dana-Farber Cancer Institute (Boston, MA, USA), led by Dr. Loren Walensky, developed a new compound, known as a stapled BIM BH3 peptide, which was found to competitively bind with antiapoptotic proteins and led to enhanced apoptosis in cancer cells. They also revealed that tumor growth in mice was blocked by the stapled BIM BH3 compound and that the new compound worked synergistically with other with pharmaceutical agents that stimulate apoptosis.

The potential therapeutic effects of stapled BIM BH3 were further shown by activation of cell death in an acute myeloid leukemia tumor model in mice with little side effects on surrounding tissue. This study presents a new formulation of a BH3 mimetic that has wide BCL-2 family targeting and may provide considerable clinical benefit.

Related Links:
Dana-Farber Cancer Institute