Biomarker-guided combination therapy targets subtype of advanced prostate cancer

MD Anderson Research Highlight May 13, 2025

Castration-resistant prostate cancer (CRPC) remains one of the most lethal and treatment-resistant forms of prostate cancer, highlighting a need to identify reliable biomarkers to predict therapy response.  Researchers led by Feiyu Chen, Ph.D., and Di Zhao, Ph.D., used genetic models and multi-omics approaches to identify a key mechanism driving hormone therapy resistance in a specific prostate cancer subtype. They also developed a promising treatment strategy for patients whose tumors carry dual alterations in the genes CHD1 and SPOP. The study showed that loss of CHD1 rewires tumor metabolism, increasing cholesterol biosynthesis and enabling prostate cancer cells to produce androgen. This allows cancer to bypass standard anti-androgen therapy and continue growing. A combination of anti-androgen therapy with cholesterol-lowering drugs — both already approved by the Food and Drug Administration — produced strong and lasting anti-tumor effects in preclinical models. This suggests a potential new, personalized treatment approach for patients with CRPC carrying these genetic changes. Learn more in Nature Cancer.