Cancer

Cell culture and mouse studies suggest inhibiting BRD4 or CDK7 could help treat diffuse intrinsic pontine glioma (DIPG). In DIPG cells from eight patients, a bromodomain inhibitor tool compound or a CDK7 inhibitor tool compound decreased viability compared with no treatment. In tumor cells from four of the patients, the pan-deacetylase (DAC) inhibitor Farydak panobinostat plus either tool compound decreased cell viability compared with any of the agents alone. In two orthotopic patient-derived xenograft (PDX) mouse models of DIPG, knockdown of BRD4 decreased tumor burden compared with normal BRD4 expression and in one model, BRD4 knockdown increased survival. In one of the PDX models and another orthotopic PDX mouse model of DIPG, the CDK7 inhibitor tool compound decreased tumor burden compared with vehicle. In the orthotopic model, the CDK7 inhibitor tool compound increased survival. Next steps could include identifying and testing BRD4 or CDK7 inhibitors in additional models of DIPG.

Novartis AG markets Farydak panobinostat to treat multiple myeloma (MM) and has the compound in Phase I through Phase III testing to treat other cancers, glycosphingolipid storage disorders and sickle cell disease...