论文部分内容阅读
耐药性是癌症治疗中的主要挑战，已成为恶性肿瘤临床治疗的难点。YAP/TAZ作为Hippo信号通路下游效应因子，参与多种抗肿瘤治疗的耐药模式，可通过激活生长因子信号、抑制凋亡、调节DNA损伤反应，促进细胞周期、诱导干细胞样特性、诱导间充质转化，引起抗肿瘤治疗过程中的耐药作用。YAP信号的失控可能是对肿瘤细胞各种靶向、化学疗法及放疗产生内在和获得性耐药的主要机制。此外，YAP还可通过Hippo经典通路外的非转录激活作用与多种蛋白相互作用，诱导肿瘤耐药的发生。YAP蛋白表达状态可作为一项预测肿瘤放化疗敏感性、判断肿瘤预后的指标，其抑制剂与放化疗联合应用，是潜在的肿瘤耐药的治疗靶点。旨在简要概述导致治疗耐药的YAP依赖性机制，为解决肿瘤治疗耐药的潜在策略提供观点。“,”Drug resistance is the main challenge in cancer treatment and has become a difficulty in the clinical treatment of malignant tumors. YAP/TAZ, as a downstream effector of the Hippo signaling pathway, participates in a variety of anti-tumor treatment resistance modes. It can activate growth factor signals, inhibit apoptosis, regulate DNA damage response, promote cell cycle, induce stem cell-like characteristics, induce mesenchymal transformation, and cause drug resistance in the process of anti-tumor therapy. The uncontrolled YAP signal may be the main mechanism of internal and acquired resistance to various targeting, chemotherapy and radiotherapy of tumor cells. In addition, YAP can also interact with a variety of proteins through non-transcriptional activation outside the Hippo classic pathway to induce tumor resistance. The expression status of YAP protein can be used as an indicator to predict the sensitivity of tumor radiotherapy and chemotherapy and judge the prognosis of tumors. The combination of its inhibitors and radiotherapy and chemotherapy is a potential therapeutic target for tumor resistance. In this paper, the YAP-dependent mechanisms that lead to therapeutic resistance was briefly reviewed in order to provide perspectives on potential strategies to address tumor resistance.