Findings from a new study led by Yale Cancer Center shows the small molecule inhibitor drug, PF05175157, originally developed to treat diabetes by Pfizer, may help in the treatment of breast cancer. The findings were reported today at the 2021 San Antonio Breast Cancer Symposium in San Antonio, Texas.
“Our research shows the preclinical, anti-cancer activity using PF05175157 may lead us to bring this drug back into the clinic to help treat patients with breast cancer,” said lead study author Julia Foldi, MD, PhD, a clinical fellow at Yale Cancer Center and Smilow Cancer Hospital. “More studies are needed, but our initial data looks very promising.”
Cancer cells are characterized by altered metabolism. In this study, the Yale team identified new metabolic vulnerabilities in cancer cells that are based on a loss of enzyme diversity. They found that an enzyme called acetyl-CoA-carboxylase-1 (ACC1), is critical for the survival of breast cancer cells. The ACC1 enzyme is the key initial step in fatty acid synthesis. Fatty acids are building blocks of the various types of lipids and fat that are the critical ingredients of cell membranes and play an important role in energy generation in cells. In their analysis, the team showed that blocking ACC1 using PF05175157 can inhibit the growth of breast cancer cells grown in mice and also in a patient derived cancer models.
“We are currently testing this drug in combination with other approved breast cancer drugs to see if it could improve their activity, with the hope to bring the most promising combinations to the clinic to help patients with breast cancer,” added Lajos Pusztai, MD, DPhil, Professor of Medicine (Medical Oncology), Director of Breast Cancer Translational Research at Yale Cancer Center, and senior author of the study.
Funding for the study was provided by a leadership grant from the Susan G. Komen Foundation.