The study find that the patients with the most common form which tests positive for hormone receptors (HR+) and negative for the HER2 receptor usually respond well to treatment. But for those in advanced stages, few treatment options existed until the recent emergence of a new class of drugs known as CDK4/6 inhibitors. These inhibitors showed remarkable efficacy in blocking tumor growth, halting disease progression and boosting survival; leading the FDA to fast-track the approval of three such drugs to date. Today, they are used as frontline medications for patients with advanced, HR+/HER2- breast cancers.

Few treatment options existed

While these drugs have the same biological targets and are often used interchangeably; but a growing body of evidence suggests they have important underlying differences. But Now; Harvard Medical School researchers based in the Laboratory of Systems Pharmacology at the Blavatnik Institute and the Massachusetts General Hospital ; have carried out the first head-to-head comparison of the three currently approved CDK4/6 inhibitors in breast cancer cell lines and animals.

Their findings, published Aug. 15 in Cell Chemical Biology; reveal significant and thus far poorly understood differences in biological activity among members of a drug class designated as breakthrough therapies by the FDA. One inhibitor in particular abemaciclib exhibited unique ;and potentially advantageous therapeutic activity that could help inform the design of better treatment strategies; but including optimized combination therapies and circumventing drug resistance; the authors said.

Potentially advantageous therapeutic

“Despite the sophistication of industrial drug discovery, the activities of many drugs are not fully understood; at the time of their approval by the FDA;” said senior study author Peter Sorger; the HMS Otto Krayer Professor of Systems Pharmacology in the HMS Department of Systems Biology and director of the Laboratory of Systems Pharmacology. “In this case; it appears that the drug abemaciclib may unexpectedly work in patients who are not responsive to other drugs in the class.”

In their study, Sorger and colleagues, spearheaded by co-first authors Marc Hafner and Termeer Fellow Caitlin Mills; partnered with investigators based at the Termeer Center for Targeted Therapies at Mass General to form a cross-disciplinary team with the basic science and clinical expertise needed to comprehensively ; compare the drugs Characterizing the exact target inhibition profile and the biological effects of these therapeutic agents is essential; because in some instances these differences may explain why one works and why another doesn’t. Therefore  Thorough and carefully designed studies are the only way to understand how best to sequence or combine these transformative drugs; and to identify which will be most beneficial for any individual patient.” Study co-senior author Dejan Juric; director of the Termeer Center