PTPN11型
MAPK/ERK通路
癌症研究
癌变
蛋白质酪氨酸磷酸酶
癌症
变构调节
癌基因
生物
信号转导
医学
细胞周期
遗传学
克拉斯
结直肠癌
受体
作者
Alexander Scheiter,Li‐Chun Lu,Lilian H. Gao,Gen–Sheng Feng
标识
DOI:10.1146/annurev-cancerbio-062722-013740
摘要
The nonreceptor tyrosine phosphatase SHP2 has been at the center of cell signaling research for three decades. SHP2 is required to fully activate the RTK/RAS/ERK signaling cascade, although the underlying mechanisms are not completely understood. PTPN11, which encodes SHP2, is the first identified proto-oncogene that encodes a tyrosine phosphatase, with dominantly activating mutations detected in leukemias and solid tumors. However, SHP2 has pro- and antioncogenic effects, and the most recent data reveal opposite activities of SHP2 in tumor cells and microenvironment cells. Allosteric SHP2 inhibitors show promising antitumor effects and overcome resistance to inhibitors of RAS/ERK signaling in animal models. Many clinical trials with orally bioactive SHP2 inhibitors, alone or combined with other regimens, are ongoing for a variety of cancers worldwide, with therapeutic outcomes yet unknown. This review discusses the multifaceted functions of SHP2 in oncogenesis, preclinical studies, and clinical trials with SHP2 inhibitors in oncological treatment.
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