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

Recently, Dr. Chandarlapaty and his team have focused on how breast cancer develops resistance to a class of drugs commonly used to treat advanced estrogen receptor (ER)-positive breast cancer, CDK4/6 inhibitors. They have discovered that a set of proteins called APOBEC3 enzymes are a frequent cause of drug resistance in breast cancer. Drugs that block the activity of these enzymes could keep cancer in check longer – or prevent relapse.

What’s next

While antibody drug conjugates (ADCs) have proven to be a very effective treatment, resistance can develop over time. Dr. Chandarlapaty and his team will further investigate resistance mechanisms of a specific ADC, trastuzumab deruxtecan (Enhertu®). Their results will help move us closer to more effective treatments that can block tumor evolution and prevent the development of drug resistance.