Study Supports Evidence that Rab Disruption May Be Effective Strategy for Treating Multiple Myeloma

Roswell Park research to be presented at AACR annual meeting in New Orleans
Wednesday, April 20, 2016

BUFFALO, N.Y. — 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.”

This research is supported, in part, by the National Cancer Institute, or NCI (project no. R01CA172070).

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The mission of Roswell Park Cancer Institute (RPCI) is to understand, prevent and cure cancer. Founded in 1898, RPCI is one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. The Institute is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit www.roswellpark.org, call 1-877-ASK-RPCI (1-877-275-7724) or email askrpci@roswellpark.org. Follow Roswell Park on Facebook and Twitter.

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