Treatments may be used not only to treat and to control the myeloma itself, but also to ease symptoms and complications of the myeloma. Radiotherapy, Bisphosphonates, and Other Supportive Therapies would bring about adverse effects, Such as bone pain and fractures. Thus, developing effective therapies against multiple myeloma (MM) is a pending challenge.
PI3K activation may be correlated with tumor progression and drug resistance, and inhibiting PI3K can induce apoptosis in MM cells. Therefore, inactivation of PI3K is predicted to increase the susceptibility of MM to anticancer therapy. Glauer J, et al demonstrated that a novel class of PI3K inhibitors, BAY80-6946, was highly efficacious in four different MM cell lines, where it induced significant antitumoral effects in a dose-dependent manner. The compound inhibited cell cycle progression and increased apoptosis, and showed convincing in vivo activity against the human AMO-1 and MOLP-8 myeloma cell lines in a preclinical murine model.
Additionally, Munugalavadla V et al indicated that the PI3K inhibitor GDC-0941, combined with existing clinical regimens, exhibited superior activity in multiple myeloma. In vitro, GDC-0941 was synergized with dexamethasone and lenalidomide; in vivo GDC-0941 had anti-myeloma activity and significantly increased the activity of the standard of care agents in several murine tumor models.
These data provide a clear therapeutic prospect for the inhibition of PI3K and provide a rationale for clinical development of GDC-0941 in myeloma.