Cancer

Cell and mouse studies suggest promoting PMAIP1 expression or inhibiting MCL1 could enhance the efficacy of BCL-2 inhibitors to treat diffuse large B cell lymphoma (DLBCL). In a DLBCL cell line, a tool compound BCL-2 inhibitor plus overexpression of PMAIP1, which binds MCL1 to promote apoptosis, increased cell death compared with the BCL-2 inhibitor and normal PMAIP1 expression. In a xenograft mouse model of DLBCL, the BCL-2 inhibitor combined with either Farydak panobinostat, which indirectly up-regulates PMAIP1, or an MCL1 inhibitor tool compound decreased tumor growth compared with any agent alone. Next steps could include identifying and testing PMAIP1 inhibitors in combination with BCL-2 inhibitors in DLBCL models.

Novartis AG markets Farydak, an oral pan-deacetylase (DAC) inhibitor, for multiple myeloma (MM) and has the compound in Phase III testing for Hodgkin disease and Phase II testing for acute myelogenous leukemia (AML) and prostate cancer...