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Merck
  • 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.

Cell death & disease (2022-12-13)
Ying Zhang, Wei Wei, Changying Li, Siyuan Yan, Shanshan Wang, Shudong Xiao, Chenchen He, Jing Li, Zhi Qi, Benyi Li, Kuo Yang, Changlin Li
摘要

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 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 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.

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