热疗是继手术、放疗、化疗、生物治疗后又一种重要的肿瘤治疗方法，它能直接杀伤肿瘤，抑制新生血管，降低肿瘤的侵袭转移，已被广泛用于肿瘤的治疗。由于肿瘤对热疗易产生耐热性，单独应用热疗的治疗效果仍然不够理想，所以迫切需要寻找增加热疗敏感性的靶点或方法以增强热疗的抗肿瘤作用。在前期工作中，我们发现热疗能够诱导肿瘤中癌基因STAT3的激活，在应用STAT3抑制剂干预后，肿瘤对热疗的敏感性显著增加，表现出良好的抗肿瘤作用，提示STAT3可能与热疗的耐热性有关，是消除肿瘤耐热性，增敏热疗抗肿瘤作用的潜在靶点。本项目拟在前期工作的基础上，以筛选STAT3相互作用差异蛋白为核心，构建热疗诱导肿瘤中STAT3激活的信号通路，阐明STAT3抑制剂增加热疗敏感性的机制，并探讨以热疗-STAT3通路中关键节点分子为靶点进行肿瘤治疗的可行性，为筛选热疗的增敏靶点提供理论依据，为发展新的、有效的热疗治疗方案提供新思路。

Hyperthermia is thought to be one of the important cancer therapies following surgery, radiation therapy, chemotherapy and biotherapy, which has been widely used in a variety of tumors. It can damage and kill the tumor cell, inhibit angiogenesis, reduce tumor invasion and metastasis. However, the therapeutic effect of hyperthermia alone is still not ideal due to the thermotolerance produced by tumors.So,there is an urgent need to screen some novel targets or methods which could increase the sensitivity of tumors to hyperthermia to get a better anti-tumor effects. Results from the preliminary studies showed that hyperthermia could induce the activation of STAT3 in tumors. After the intervention of STAT3 inhibitor, the sensitivity of tumors to hyperthermia was significantly increased, and showed an ideal therapeutic effects invivo. It is suggested that STAT3 may be a novel molecule involved in the production of thermotolerance, and a potential target which could eliminate the thermotolerance to enhance the sensitivity of tumors to hyperthermia. This project aimed to identify the differential interacting proteins with STAT3, and to clarify the STAT3 signaling pathway induced by hyperthermia and the anti-tumor mechanism of intervention therapy of STAT3 inhibitor. Futhermore, the fesibility of cancer therapy by targetting the key molecules in the hyperthermia- - STAT3 signaling pathway will also be explored.The implementation of this innovative project will not only provide a theoretical instruction for screening the targets to enhance the anti-tumor effects of hyperthermia, but aslo provide some new and effective ideas for hyperthermia application in clinical trail.