A multi-institutional research team has identified what may be a novel mechanism underlying acquired resistance to CDK 4/6 inhibitor treatment for breast cancer. In their report published in the Annals of Oncology, the team – led by investigators at Massachusetts General Hospital (MGH), Institute Gustave Roussy in Paris, and Texas Oncology-Baylor Sammons Cancer Center/U.S. Oncology in Dallas – reports their discovery of new mutations in the RB1 gene, a key part of the pathway targeted by CDK 4/6 inhibitors, in women with hormone-receptor (HR)-positive breast cancer whose tumors had progressed on CDK 4/6 inhibitor treatment. Proofs of this study were made available online in December 2017, ahead of print publication in March 2018.
“CDK 4/6 inhibitors have changed the treatment landscape for HR-positive breast cancer, and it is estimated that more than 70,000 patients in the U.S. have been treated with palbociclib, the first of three such drugs to receive FDA approval,” says Aditya Bardia, MD, MPH, of the MGH Cancer Center, co-senior author of the study. “However, after months of responding to treatment, patients’ tumors eventually progress. The mechanisms governing the development of resistance have been unknown, and this first report of the emergence of RB1 mutations by
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