C-Met as a potential target for the treatment of gastrointestinal cancer: Current status and future perspectives

被引:68
作者
Bahrami, Afsane [1 ,2 ]
Shahidsales, Soodabeh [3 ]
Khazaei, Majid [4 ,5 ]
Ghayour-Mobarhan, Majid [6 ]
Maftouh, Mina [6 ]
Hassanian, Seyed Mahdi [6 ,7 ]
Avan, Amir [6 ]
机构
[1] Mashhad Univ Med Sci, Mol Med Grp, Dept Modern Sci & Technol, Mashhad, Iran
[2] Mashhad Univ Med Sci, Student Res Ctr, Fac Med, Mashhad, Iran
[3] Mashhad Univ Med Sci, Sch Med, Canc Res Ctr, Mashhad, Iran
[4] Mashhad Univ Med Sci, Neurogen Inflammatory Res Ctr, Mashhad, Iran
[5] Mashhad Univ Med Sci, Dept Physiol, Mashhad, Iran
[6] Mashhad Univ Med Sci, Sch Med, Metab Syndrome Res Ctr, Mashhad, Iran
[7] Mashhad Univ Med Sci, Sch Med, Dept Med Biochem, Mashhad, Iran
关键词
c-Met/HGF pathway; c-Met inhibitors; resistance to targeted agents; upper gastrointestinal cancers; HEPATOCYTE GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; TIVANTINIB ARQ 197; CELL LUNG-CANCER; ADVANCED HEPATOCELLULAR-CARCINOMA; PRIMARY COLON-CANCER; GASTRIC-CANCER; FACTOR/SCATTER FACTOR; TUMOR-GROWTH; ACQUIRED-RESISTANCE;
D O I
10.1002/jcp.25794
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
Aberrant activation of the HGF/c-Met signalling pathways is shown to be related with cell proliferation, progression, metastasis, and worse prognosis in several tumor types, including gastrointestinal cancers, suggesting its value as a stimulating-target for cancer-therapy. Several approaches have been developed for targeting HGF and/or c-Met, and one of them, crizotinib (dual c-Met/ALK inhibitor), is recently been approved by FDA for lung-cancers with ALK-rearrangement. The main aim of current review is to give an overview on the role of c-Met/HGF pathway in gastrointestinal cancer, in preclinical and clinical trials. Although several important matters is still remained to be elucidated on the molecular pathways underlying the antitumor effects of this therapy in gastrointestinal-cancers. Further investigations are warranted to recognize the main determinants of the activity of c-Met inhibitors, for parallel targeting signalling pathway associated/activated via MET/HGF pathway or in response to the cell resistance to anti-c-Met agents. Additionally, identification of patients that might benefit from therapy could help to increase the selectivity and efficacy of the therapy.
引用
收藏
页码:2657 / 2673
页数:17
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