Upstate researchers find key cellular enzyme could be effective drug target in urologic cancer cells
SYRACUSE, N.Y.-- Researchers 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.
Ongoing research into treatments for kidney cancer is especially important since kidney cancer is known to be resistant to current chemotherapy and radiation.
In this study, 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 role is to help cancer cells grow and thrive. This disruption is essential to halt the growth and kill the cancer cells.
Previous research showed that the disruption of Hsp90 from its activator, Aha1, sensitizes cancer cells to Hsp90 drugs. The Upstate researchers used specific compounds aiming 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, leukemia (multiple myeloma) and gastric cancer.
Upstate’s 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.
Their findings appear in Cell Reports.
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."
The scientific community is working with measured enthusiasm studying and testing ways to disrupt Hsp90’s role as a guardian of cancer cells, thereby enabling cancer survival. The research was conducted at Upstate and used kidney tumors from patients that were treated by urologic surgeons at Upstate Urology.
About 61,000 new cases of kidney cancer are diagnosed each year, with about 14,000 people dying from the disease. The most common form of kidney care is renal cell carcinoma, which is resistant to chemotherapy. Mollapour says, “this type of study brings Hsp90 drugs closer to a clinical trial testing in kidney cancer patients.”
Caption: The research team from Upstate Medical University, includes, from left, Mehdi Mollapour, Ph.D., an assistant professor of urology and biochemistry and molecular biology; Diana Dunn, a graduate student; and Mark Woodford, a research assistant; Dimitra Bourboulia, Ph.D., an assistant professor; and Gennady Bratslavsky, M.D., professor and chair of urology.