Cellular Enzyme Key to Disrupting Cancer Cell Growth

New approach may stop growth and kill cancer cells.

Researchers at the SUNY Upstate Medical University have discovered a potential drug target in cancer cells for urologic cancers. The target, a key cellular enzyme called c-Abl, is of particular interest to researchers trying to find an alternative treatment to kidney cancer, which is resistant to chemotherapy and radiation.

The study uncovered a mechanism that could disrupt or disengage Heat Shock Protein 90 (Hsp90) from its role as chaperone of cancer cells. What is meant by the “chaperone” role of Hsp90 is that it acts to protect cancer cells so that they can grow and thrive. Disrupting this protein is essential to stopping growth and killing cancer cells.

Previous studies have shown that the disruption of Hsp90 from its activator, Aha1, sensitizes cancer cells to Hsp90 drugs. Researchers attempted to disconnect Aha1 from Hsp90 by attacking the regulator of Aha1, c-Abl1, with specific compounds.

With c-Abl1 disrupted, researchers were able to prove that Hsp90 drugs can be used more effectively in inhibiting kidney cancer cell growth. Hsp90 drugs were previously tested in clinical trials for breast cancer, lung cancer, leukemia, and gastric cancer.

According to Mehdi Mollapour, PhD, an assistant professor of urology and biochemistry and molecular biology, the findings of the 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 continues to search for other ways of disrupting Hsp90 from acting as a protector of cancer cells, allowing cancer survival. The current study was conducted using human kidney tumors from patients treated by urologic surgeons at Upstate Urology.

The study brings Hsp90 drugs closer to a clinical trial in kidney cancer patients, according to Mollapour.