Idarubicin combats abiraterone and enzalutamide resistance in prostate cells via targeting XPA protein

Idarubicin combats abiraterone and enzalutamide resistance in prostate cells via targeting XPA protein

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Abstract Although second-generation therapies like abiraterone (ABI) and enzalutamide (ENZ) benefit patients with castration-resistant prostate cancer (CRPC), drug resistance frequently occurs, eventually resulting in 20Amp Mains Plug Top therapy failure.In this study, we used two libraries, FDA-approved drug library and CRISP/Cas9 knockout (GeCKO) library to screen for drugs that overcome treatment resistance and to identify the potential drug-resistant genes involved in treatment resistance.Our screening results showed that the DNA-damaging agent idarubicin (IDA) overcame abiraterone and Soprano Ukulele enzalutamide resistance in prostate cancer cells.

IDA treatment inhibited the DNA repair protein XPA expression in a transcription-independent manner.Consistently, XPA knockout sensitized prostate cancer cells to abiraterone and enzalutamide treatment.In conclusion, IDA combats abiraterone and enzalutamide resistance by reducing XPA protein level in prostate cancer.