SHP2特性及其变构抑制剂SHP099肿瘤免疫治疗的研究进展

Research progress on characteristics of SHP2 and its inhibitor SHP099 in tumor immunotherapy

SHP2作为细胞内信号转导的关键分子,由PTPN11基因编码,在体内广泛分布并参与细胞正常生理功能调节。基于PTPN11为编码酪氨酸磷酸酶的原癌基因,SHP2成为参与肿瘤发生发展的又一研究热点,以SHP2为靶点的多种抑制剂和变构剂亦应运而生。SHP2小分子变构抑制剂SHP099单独使用,或与MEK抑制剂和PD-1单抗等联用在多项研究中展示了良好的抗肿瘤效果,但同时SHP099对肿瘤突变株的选择性作用也不容忽视。因此,深入探讨SHP2的分子特性及其抑制剂和变构剂的基础实验及临床应用效果,可为肿瘤靶向免疫治疗提供新的方向。

As a key molecule of intracellular signal transduction,SHP2,encoded by PTPN11 gene,is widely distributed in body and involved in normal physiological functions of cells. Based on role of PTPN11 as a proto-oncogene encoding tyrosine phosphatase,SHP2 has become another research hotspot involved in tumor genesis and development,and various inhibitors and allosteric agents targeting SHP2 have emerged. SHP099,a small molecule allosteric inhibitor of SHP2,alone or in combination with MEK inhibitor and PD-1 monoclonal antibodies,has shown promising anti-tumor effects in multiple studies,but selective effect of SHP099 on tumor mutants should not be overlooked. Therefore,further exploration of molecular characteristics of SHP2 and its inhibitors and allosteric agents in both fundamental experiments and clinical application could provide new research directions for targeted immunotherapy.