Nguyen Chan D K, Yi Chunling
Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
Trends Cancer. 2019 May;5(5):283-296. doi: 10.1016/j.trecan.2019.02.010. Epub 2019 Mar 27.
Drug resistance is a major challenge in cancer treatment. Emerging evidence indicates that deregulation of YAP/TAZ signaling may be a major mechanism of intrinsic and acquired resistance to various targeted and chemotherapies. Moreover, YAP/TAZ-mediated expression of PD-L1 and multiple cytokines is pivotal for tumor immune evasion. While direct inhibitors of YAP/TAZ are still under development, FDA-approved drugs that indirectly block YAP/TAZ activation or critical downstream targets of YAP/TAZ have shown promise in the clinic in reducing therapy resistance. Finally, BET inhibitors, which reportedly block YAP/TAZ-mediated transcription, present another potential venue to overcome YAP/TAZ-induced drug resistance.
耐药性是癌症治疗中的一项重大挑战。新出现的证据表明,YAP/TAZ信号通路失调可能是对各种靶向治疗和化疗产生固有耐药性和获得性耐药性的主要机制。此外,YAP/TAZ介导的PD-L1和多种细胞因子的表达对于肿瘤免疫逃逸至关重要。虽然YAP/TAZ的直接抑制剂仍在研发中,但已获美国食品药品监督管理局(FDA)批准的间接阻断YAP/TAZ激活或YAP/TAZ关键下游靶点的药物在临床上已显示出降低治疗耐药性的前景。最后,据报道可阻断YAP/TAZ介导转录的溴结构域和额外末端结构域(BET)抑制剂是克服YAP/TAZ诱导的耐药性的另一个潜在途径。