Key Cellular Enzyme found that could be Effective Drug Target for Urologic Cancer Cells

Clear_cell_renal_cell_carcinoma_high_mag_croppedResearchers at the SUNY Upstate Medical University have found that a key cellular enzyme, c-Abl, could be an effective drug target in cancer cells for urologic cancers, such as prostate and kidney.

Currently kidney cancer is known to be resistant against chemotherapy and radiation. About 61,000 new cases of kidney cancer are diagnosed each year, with about 14,000 people dying from the disease making this breakthrough quite significant.

Researchers uncovered a mechanism whereby the Heat Shock Protein 90, or Hsp90, could be disrupted or disengaged from its role as chaperone of cancer cells. By acting as a guardian of cancer cells, Hsp90’s role is to help cancer cells grow and thrive. Therefore this disruption is essential to halt the growth and kill the cancer cells.

Previous research had showed that the disruption of Hsp90 from its activator, Aha1, sensitises cancer cells to Hsp90 drugs. The Upstate researchers used specific compounds aimed at the regulator of Aha1, known as c-Abl1, to successfully disconnect Aha1 from Hsp90. With the regulator Aha1 disrupted, researchers were able to show that Hsp90 drugs can be used more effectively in inhibiting kidney cancer cells growth. Hsp90 drugs have been tested successfully in clinical trials for breast cancer, lung cancer, leukaemia (multiple myeloma) and gastric cancer.

The research was led by Mehdi Mollapour, Ph.D., an assistant professor of urology and biochemistry and molecular biology; Diana Dunn, a graduate student in the laboratory; and Mark Woodford, a research assistant; and was completed in collaboration with Dimitra Bourboulia, Ph.D., an assistant professor; and Gennady Bratslavsky, M.D., professor and chair of urology, all at Upstate Medical University.

According to Mollapour, the findings of this study will not only “help enhance the efficacy of Hsp90 drugs in the clinic, but also lay a foundation for future studies aiming to understand combination therapy with Hsp90 drugs.”


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