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Targeting the ‘undruggable’: New molecular degraders offer hope for aggressive breast cancer

In the battle against aggressive breast cancer, a once-elusive target is now within reach—thanks to a breakthrough from a team from the Faculty of Medicine at Hebrew University. Dr. Raphael Benhamou and M.Sc. student Liann Kassabri have developed innovative druglike molecules capable of degrading HuR, a key RNA-binding protein that stabilizes oncogenes and fuels cancer progression.

HuR (also known as ELAVL1) has long been labeled “undruggable” due to its structural flexibility and lack of a conventional active site. Overexpressed in many cancer types—particularly breast cancer—HuR fortifies by protecting mRNAs that drive and survival.

“We knew that simply blocking HuR wasn’t enough,” says Dr. Benhamou. “We needed to eliminate it altogether.” Strikingly, this elimination led to a three to four orders of magnitude improvement in anticancer properties compared to traditional HuR-binding molecules that do not induce degradation.

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