Rab inhibition may be a promising antimyeloma strategy

Roswell Park Cancer Institute (RPCI) researchers are investigating agents that target and disrupt the trafficking of monoclonal antibodies in multiple myeloma, a cancer of the bone marrow. The results will be presented at the American Association for Cancer Research (AACR) Annual Meeting 2016, to be held April 16-20 in New Orleans.

Kaitlyn Dykstra, PhD, a postdoctoral fellow in the Department of Medicine at Roswell Park, is the first author and Sarah Holstein, MD, PhD, an Associate Professor of Oncology in that department, is the senior author of "Determination of Rab GTPase-mediated pathways critical for the anti-myeloma activity of Rab GGTase inhibitors" (abstract 4768), to be presented on Wednesday, April 20 at 8 a.m. CDT.

Approximately 30,000 new cases of multiple myeloma, a relatively uncommon cancer, will be diagnosed in 2016. This cancer is characterized by excessive production of nonspecific monoclonal antibodies. Roswell Park researchers have previously demonstrated that inhibiting a family of proteins called RabGTPases, or Rabs, disrupts the secretion of the monoclonal protein, causing the myeloma cells to be stressed and die.

In this study, the scientists report that incapacitating individual Rab proteins was sufficient to partially disrupt the trafficking of the monoclonal protein, but did not cause cell death. Further research will determine whether a more complete knockdown of the individual Rabs or the knockdown of multiple Rabs is necessary for tumor cell death.

"The last few years have seen exciting, encouraging progress in development of new therapies for multiple myeloma, but we're still looking for more effective and longer-lasting treatment approaches," notes Dr. Holstein, a clinician with the lymphoma/myeloma service at Roswell Park. "Our findings suggest that Rab inhibition is a novel and promising antimyeloma strategy that merits further investigation."