Julian Adams, PhD, the president of research and development at Infinity Pharmaceuticals, describes the mechanism of action for the experimental PI3 kinase delta/gamma inhibitor IPI-145 in hematologic malignancies.
PI3 kinase, specifically the delta and gamma isoforms, are expressed ubiquitously on cells associated with the immune system, specifically B cells, T cells, and cells of myeloid origin. In general, Adams notes, PI3 kinase is the master regulator of cellular activation, proliferation, survival, and intracellular trafficking. It is utilized by hematologic malignancies for trafficking into the lymph cells, where the cancer survives.
Inhibiting PI3 kinase delta/gamma forces the cancer cells out of the lymph node microenvironment, Adams suggests. Once blocked from the lymph cells, the cancer is restricted to the peripheral blood, where it dies.
Ruxolitinib, a JAK1/2 inhibitor, is the first treatment to demonstrate efficacy in a phase III trial for patients with polycythemia vera (PV), a chronic, incurable blood cancer with limited treatment options