Department for BioMedical Research, Inselspital, Bern University Hospital, and University of Bern, 3008, Bern, Switzerland.
Department of Radiation Oncology, Inselspital, Bern University Hospital, and University of Bern, 3010, Bern, Switzerland.
Oncogene. 2020 Apr;39(14):2845-2862. doi: 10.1038/s41388-020-1193-8. Epub 2020 Feb 7.
MET, the receptor tyrosine kinase (RTK) for hepatocyte growth factor, is a proto-oncogene involved in embryonic development and throughout life in homeostasis and tissue regeneration. Deregulation of MET signaling has been reported in numerous malignancies, prompting great interest in MET targeting for cancer therapy. The present review offers a summary of the biology of MET and its known functions in normal physiology and carcinogenesis, followed by an overview of the most relevant MET-targeting strategies and corresponding clinical trials, highlighting both past setbacks and promising future prospects. By placing their efforts on a more precise stratification strategy through the genetic analysis of tumors, modern trials such as the NCI-MATCH trial could revive the past enthusiasm for MET-targeted therapy.
MET,肝细胞生长因子的受体酪氨酸激酶(RTK),是一种参与胚胎发育和整个生命周期的内稳态和组织再生的原癌基因。MET 信号的失调已在许多恶性肿瘤中被报道,这促使人们对 MET 靶向治疗癌症产生了极大的兴趣。本综述概述了 MET 的生物学及其在正常生理和肿瘤发生中的已知功能,随后概述了最相关的 MET 靶向策略及其相应的临床试验,强调了过去的挫折和有前途的未来前景。通过对肿瘤进行基因分析,采用更精确的分层策略,现代试验如 NCI-MATCH 试验,可以恢复过去对 MET 靶向治疗的热情。