Cancer’s accomplice: Targeting a protein to treat kidney cancer

UrologyResearchGroup

The research team from Upstate includes, from left, Mehdi Mollapour, PhD, an assistant professor of urology and biochemistry and molecular biology; Diana Dunn, a graduate student; and Mark Woodford, a research assistant; Dimitra Bourboulia, PhD, an assistant professor; and Gennady Bratslavsky, MD, professor and chair of urology. (PHOTO BY DEBORAH REXINE)

BY AMBER SMITH

A protein called Hsp90 chaperones cancer cells, allowing them to grow and thrive.

Scientists around the world have been working with measured enthusiasm on how to disrupt Hsp90. This involves figuring out the mechanics of Hsp90, how best to get to the protein, and which medication can restrain Hsp90’s ability to assist cancer.

Scientists at Upstate – using tissue samples from patients who underwent kidney surgery at Upstate University Hospital – have helped answer some of the questions.

Renal cell carcinomas are the most common type of kidney cancer, a disease that affects mostly older men and women. Unfortunately, these cancers are resistant to chemotherapy, explains Mehdi Mollapour, PhD, an assistant professor of urology and biochemistry and molecular biology.

That’s why researchers are focused on finding other strategies to halt the growth of and kill kidney cancer cells. What they learn can also inform how other types of cancer cells are killed.

Previous research has shown that keeping the Hsp90 protein away from another protein chaperone called Aha1 helps sensitize cancer cells to drugs that can inhibit Hsp90. The question was how to accomplish that reliably.

Mollapour’s team of scientists found a way, using specific compounds to kill a hyperactive enzyme called c-Abl, which regulates Aha1. With Aha1 successfully separated from Hsp90, the Upstate scientists were able to show that Hsp90 drugs can be used more effectively to inhibit kidney cancer cell growth.

Building on that research project, the team used tissue samples granted by patients who underwent partial or total kidney removal at Upstate in recent years. Working with an investigational medication designed to inhibit Hsp90, the scientists showed that with Aha1 separated from Hsp90, the drug accumulates in the tumor cells, but not in healthy kidney cells.

“This was a big finding,” Mollapour says. “Fundamentally we finally managed to find the answer to why this drug accumulates in the tumors and not the normal cells.” The drug modifies the tumor cells, which affects their ability to function.

Their work appears in the Feb. 2 issue of the journal Cell Reports.

“This type of study brings Hsp90 drugs closer to a clinical trial in kidney cancer patients,” Mollapour says. Such drugs have already been tested successfully in clinical trials of patients with different types of breast cancers, lung cancer, leukemia and stomach cancer.

spring16cancerThis article appears in the spring 2016 issue of Cancer Care magazine.

 

 

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