An enzyme called EZH2 has an unexpected role in driving aggressive tumor growth in treatment-resistant prostate cancers, according to a new study by scientists at Weill Cornell Medicine. The results could potentially lead to new therapies for patients with limited options and add to the significant progress the teams have made in understanding how advanced prostate cancer develops resistance to treatments that target androgen receptors. Prostate cancer is a leading cause of cancer-related death in men, claiming over 30,000 lives annually in the United States.
While most prostate cancers initially respond to androgen receptor-blocking therapies, some tumors evolve into a highly aggressive, treatment-resistant form known as neuroendocrine prostate cancer, which no longer relies on androgen signaling and is therefore difficult to treat. Understanding this transition has become a priority for researchers and clinicians. The new study, led by Drs.
Maria Diaz-Meco and Jorge Moscat, both Homer T. Hirst III Professors of Oncology in Pathology and members of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, and published Nov. 20 in Nature Communications, found that the absence of a protein called PKCλ/ι in prostate cancer cells enables EZH2 to drive aggressive growth, even with androgen receptor inhibitors present.
Normally, PKCλ/ι limits EZH2's activity. However, in PKCλ/ι-deficient cells treated with androgen receptor inhibitors, an alternative form of EZH2 .