靶向HER2的人源化抗体Herceptin是转移性乳腺癌临床治疗的一线用药。但是Herceptin单药有效性仅为12-34%，并且易产生耐药，严重影响了其疗效。Herceptin低效、易耐药的机制尚不完全清楚。多靶点联合用药可以有效地解决Herceptin低效、易耐药等问题。联合化疗药、激酶抑制剂以及其他靶点的治疗性抗体使用，可以显著地提高Herceptin的疗效。HSTC79是本课题组在前期工作中获得的HER2拮抗分子，可以抑制HER2阳性肿瘤细胞增殖、并诱导其凋亡；初步研究显示，HSTC79可以协同Herceptin发挥抗肿瘤作用。本研究拟在此基础上进一步明确该协同效应，重点阐明该协同作用的分子机制，为肿瘤的靶向治疗提供新的思路。

The humanized HER2-targeting antibody Herceptin is the first-line treatment of clinical metastatic breast cancer. However, the effectiveness of Herceptin mono-therapy is only 12-34%, and meanwhile, Herceptin treatment is easy to induce drug resistance, which seriously affects its efficacy. By now, the inefficient, resistant mechanisms of Herceptin arenot fully understood. It was considered that the multi-target combination therapy can effectively solve the above problems. In combination with chemotherapy drugs, kinase inhibitors and other therapeutic antibody against different targets can significantly improve the efficacy of Herceptin. HSTC79 is a HER2 antagonistic molecule identified by our group in previous work that can inhibit HER2-positive tumor cell proliferation and induced apoptosis. Besides, preliminary study shows that HSTC79 collaborative Herceptin showed inhanced anti-tumor effects. On this basis, this study will further clarify the synergistic effect focusing on its molecular mechanisms to provide new ideas for targeted therapy of tumors.