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Proteomics analysis of histone deacetylase inhibitor-resistant solid tumors reveals resistant signatures and potential drug combinations

   
@article{APS11044,
	author = {Bing-bing Hao and Ke Ma and Jun-yu Xu and Ru-feng Fan and Wen-si Zhao and Xing-long Jia and Lin-hui Zhai and SangKyu Lee and Dong Xie and Min-jia Tan},
	title = {Proteomics analysis of histone deacetylase inhibitor-resistant solid tumors reveals resistant signatures and potential drug combinations},
	journal = {Acta Pharmacologica Sinica},
	volume = {45},
	number = {6},
	year = {2024},
	keywords = {},
	abstract = {Histone deacetylase inhibitors (HDACis) are important drugs for cancer therapy, but the indistinct resistant mechanisms of solid tumor therapy greatly limit their clinical application. In this study we conducted HDACi-perturbated proteomics and phosphoproteomics analyses in HDACi-sensitive and -resistant cell lines using a tandem mass tag (TMT)-based quantitative proteomic strategy. We found that the ribosome biogenesis proteins MRTO4, PES1, WDR74 and NOP16 vital to tumorigenesis might regulate the tumor sensitivity to HDACi. By integrating HDACi-perturbated protein signature with previously reported proteomics and drug sensitivity data, we predicted and validated a series of drug combination pairs potentially to enhance the sensitivity of HDACi in diverse solid tumor. Functional phosphoproteomic analysis further identified the kinase PDK1 and ROCK as potential HDACi-resistant signatures. Overall, this study reveals the potential HDACi-resistant signatures and may provide promising drug combination strategies to attenuate the resistance of solid tumor to HDACi.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/11044}
}