Carlos L. Arteaga, MD

Developing new approaches to combat drug resistance and improve breast cancer outcomes.

Impact

Estrogen receptor (ER)-positive breast cancer continues to be a major cause of mortality because some of these cancers become resistant to anti-estrogen (endocrine) therapies, such as tamoxifen, aromatase inhibitors, and fulvestrant. Dr. Arteaga is conducting studies to identify the mechanisms of resistance to these drugs, which he hopes will provide the basis for the development of new approaches to improve clinical outcomes in patients with ER-positive breast cancer.

Progress Thus Far

Dr. Arteaga has identified a molecule found on the surface of ER-positive breast cancer cells that can enter the cell nucleus and regulate the genes responsible for tumor progression and resistance to endocrine therapies. He has also identified three novel resistance mechanisms to CDK4/6 inhibitors palbociclib (IBRANCE®) and abemaciclib (Verzenio®). Dr. Arteaga is conducting studies with human breast cancer cells in the laboratory that identified several additional molecular alterations associated with drug resistance. Some of these alterations are present in tumors from patients whose cancer is progressing on treatment with CDK4/6 inhibitors. However, whether these gene alterations are truly a cause of drug resistance and how to treat these cancers is unknown.

What’s next

Dr. Arteaga will continue molecular and cellular studies to discover the mechanisms by which ER-positive breast cancer cells tolerate and persist in the presence of treatment with CDK4/6 inhibitors. He speculates that those are the cancer cells that later develop full drug resistance and grow as recurrent metastases. In the next part of the project, Dr. Arteaga will develop treatment approaches with the goal of inactivating those mechanisms and reversing drug resistance.