Hidden weakness makes prostate cancer self-destruct

Cancer research · Prostate cancer

Blocking the enzymes PDIA1 and PDIA5 destabilizes the androgen receptor, leading to tumor shrinkage and cell death, and enhances the effect of the drug enzalutamide.

Scientists discovered that prostate cancer cells depend on two enzymes, PDIA1 and PDIA5, to defend their androgen receptor (AR) and sustain growth. Inhibiting either enzyme destabilizes the AR, triggers mitochondrial dysfunction, and induces oxidative stress, culminating in tumour shrinkage in cell lines and in mouse xenografts. When combined with the AR‑targeting drug enzalutamide, the therapeutic effect was markedly enhanced, suggesting a promising combination strategy for advanced disease.

Identifying PDIA1 and PDIA5 as key protectors of the androgen receptor opens a new avenue to overcome resistance to hormone‑based therapies in advanced prostate cancer and to develop combination regimens that might improve patient outcomes.

Evidence level: Sejtvonalas. Laboratóriumi sejtekben vizsgálták.

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