Researchers at Buffalo, New York-based Roswell Park Cancer Institute revealed that knocking down individual RabGTPases (Rab) proteins in myeloma cells was sufficient to disrupt the trafficking of monoclonal protein, but did not cause cell death.
The study was presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting in New Orleans. The abstract of the presentation, “Determination of Rab GTPase-mediated pathways critical for the antimyeloma activity of Rab GGTase inhibitors,” is available online here.
Multiple myeloma (MM), commonly called myeloma, is a relatively uncommon cancer formed by malignant plasma cells originating in the bone marrow. According to the American Cancer Society, 30,330 new cases of myeloma will be diagnosed in 2016 and about 2,650 deaths are expected in the United States alone.
One of the characteristics of multiple myeloma is the production of high levels of monoclonal protein (MP), which leads to an increased protein folding burden in the endoplasmic reticulum (ER) in myeloma cells and a lower threshold for cell death. The team had previously shown that inhibition of RabGTPases disrupts the secretion of MP, causing myeloma cells to stress and die.
The team further investigated how disrupting RabGTPase’s function in myeloma cells leads to apoptosis by knocking down individual Rab proteins, as there are over 60 different ones in mammalian cells.
Results revealed that incapacitating individual Rab protein partially disrupted trafficking of the monoclonal protein but did not cause cell death. Researchers now hope to understand whether a more complete knockdown of multiple Rab proteins can in fact induce myeloma 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,” senior author Dr. Sarah Holstein, a clinician with the lymphoma/myeloma service at Roswell Park, said in a news release. “Our findings suggest that Rab inhibition is a novel and promising anti-myeloma strategy that merits further investigation.”
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