背景:c-MET是一种受体酪氨酸激酶,通常被HGF激活以激活其下游信号级联,例如MAPK,PI3K/Akt/mTOR,和STAT3。c-MET调节细胞增殖,上皮-间质转化(EMT),免疫反应,形态发生,凋亡,和血管生成。c-MET已被证明在胚胎发生和早期发育中起着重要作用。c-MET途径在广泛的恶性肿瘤中失调,由于配体或受体的过度表达,基因组扩增,和MET突变。c-MET信号的失调与肿瘤进展之间的联系已得到充分证明。c-MET的过表达或过激活与不良的临床结果和对靶向治疗的获得性抗性相关。由于c-MET激活导致致癌途径的触发,废除c-MET途径被认为是癌症治疗中的关键策略。在这里,已经对c-MET通路在人类癌症中的作用及其在骨转移和治疗抗性中的相关性进行了分析.此外,已经尝试总结所选天然化合物对癌症中c-MET信号传导的抑制活性。
方法:与恶性肿瘤中c-MET途径及其天然化合物调节剂相关的出版物来自PubMed等数据库,Scopus,和谷歌学者,并根据PRISMA指南进行总结。一些用于提取相关文献的关键词是c-MET,c-MET的天然复合抑制剂,肝癌中的c-MET,乳腺癌的c-MET,肺癌的c-MET,胰腺癌中的c-MET,头颈癌的c-MET,c-MET在骨转移中,c-MET在治疗抗性中,以及c-MET抑制剂和化学治疗剂的组合。在PubChem数据库中验证了自然化合物的化学结构。
结果:搜索产生了3935种出版物,其中195份参考出版物用于我们的分析。使用ClinicalTrials.gov标识符引用临床试验。c-MET途径已被认为是对抗生长的突出目标,转移,和癌症中的化疗抗性。已经阐述了c-MET在骨转移以及治疗抗性中的关键作用。此外,已讨论了某些天然化合物在临床/临床前研究中对c-MET途径的抑制作用。
BACKGROUND: c-MET is a receptor tyrosine kinase which is classically activated by HGF to activate its downstream signaling cascades such as MAPK, PI3K/Akt/mTOR, and STAT3. The c-MET modulates cell proliferation, epithelial-mesenchymal transition (EMT), immune response, morphogenesis, apoptosis, and angiogenesis. The c-MET has been shown to serve a prominent role in embryogenesis and early development. The c-MET pathway is deregulated in a broad range of malignancies, due to overexpression of ligands or receptors, genomic amplification, and MET mutations. The link between the deregulation of c-MET signaling and tumor progression has been well-documented. Overexpression or overactivation of c-MET is associated with dismal clinical outcomes and acquired resistance to targeted therapies. Since c-MET activation results in the triggering of oncogenic pathways, abrogating the c-MET pathway is considered to be a pivotal strategy in cancer therapeutics. Herein, an analysis of role of the c-MET pathway in human cancers and its relevance in bone metastasis and therapeutic resistance has been undertaken. Also, an attempt has been made to summarize the inhibitory activity of selected natural compounds towards c-MET signaling in cancers.
METHODS: The publications related to c-MET pathway in malignancies and its natural compound modulators were obtained from databases such as PubMed, Scopus, and Google Scholar and summarized based on PRISMA guidelines. Some of the keywords used for extracting relevant literature are c-MET, natural compound inhibitors of c-MET, c-MET in liver cancer, c-MET in breast cancer, c-MET in lung cancer, c-MET in pancreatic cancer, c-MET in head and neck cancer, c-MET in bone metastasis, c-MET in therapeutic resistance, and combination of c-MET inhibitors and chemotherapeutic agents. The chemical structure of natural compounds was verified in PubChem database.
RESULTS: The search yielded 3935 publications, of which 195 reference publications were used for our analysis. Clinical trials were referenced using ClinicalTrials.gov identifier. The c-MET pathway has been recognized as a prominent target to combat the growth, metastasis, and chemotherapeutic resistance in cancers. The key role of the c-MET in bone metastasis as well as therapeutic resistance has been elaborated. Also, suppressive effect of selected natural compounds on the c-MET pathway in clinical/preclinical studies has been discussed.