Sarat Chandarlapaty, MD, PhD

Deciphering the underlying biology of drug resistance to improve patient response to targeted therapies.

Impact

Advances in cancer therapy have been a major contributor to the decline in breast cancer deaths over the last three decades. Even with these advances, however, breast cancers have the ability to evolve, adapt, and become resistant to drugs, resulting in tumor growth and metastasis to distant sites in the body, an uncurable stage of the disease. Dr. Chandarlapaty is focusing on understanding why treatments that initially are effective against breast cancer become ineffective over time, and then developing new approaches to prevent or overcome drug resistance.

Progress Thus Far

Dr. Chandarlapaty’s team has uncovered several key findings in resistance to anti-HER2 and hormone receptor-directed therapies, including a promising strategy to overcome CDK4/6 inhibitor resistance, which is currently under development for clinical use. They also identified novel mutations in the hormone receptor that prevent a response to antiestrogen therapies. His team then tested newer antiestrogen drugs for overcoming this particular form of resistance with some success and will continue to optimize the treatment. In other studies, Dr. Chandarlapaty and his colleagues are currently studying a process breast cancer cells use to coopt viral defense mechanisms making them resistant to cancer treatment and ultimately to spread to other tissues.

What’s next

His team will continue to refine their targeted approach to prevent resistance to hormone-directed therapy and delve deeper into the causation of resistance in breast cancer. As they delve into understanding how the viral defense mechanism is leveraged by breast cancer cells, they hope to devise novel treatments to overcome this process. Further, such new therapies against cancer evolution may help maintain breast cancer responsiveness to current therapies and move us closer to more resilient treatments.