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

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/...

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Detalles Bibliográficos
Autores principales: Zhang, Ying, Wei, Wei, Li, Changying, Yan, Siyuan, Wang, Shanshan, Xiao, Shudong, He, Chenchen, Li, Jing, Qi, Zhi, Li, Benyi, Yang, Kuo, Li, Changlin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9744908/
https://www.ncbi.nlm.nih.gov/pubmed/36509750
http://dx.doi.org/10.1038/s41419-022-05490-5
Descripción
Sumario: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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