C-Met as a potential target for the treatment of gastrointestinal cancer: Current status and future perspectives
Afsane Bahrami1,2, Soodabeh Shahidsales3, Majid Khazaei4
1Molecular Medicine Group, Department of Modern Sciences and Technology, Mashhad University of Medical Sciences, Mashhad, Iran.
Abstract:
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.
Insights
The HGF/c-Met pathway drives gastrointestinal cancer growth and spread. Targeting this pathway, like with crizotinib, shows promise, but further research is needed for optimal patient selection and efficacy.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Background:
- Aberrant activation of the hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (c-Met) signaling pathway is implicated in the progression and metastasis of various cancers.
- This pathway's dysregulation is particularly noted in gastrointestinal cancers, highlighting its potential as a therapeutic target.
Purpose of the Study:
- To provide a comprehensive overview of the HGF/c-Met pathway's role in gastrointestinal cancers.
- To review preclinical and clinical trial data on targeting the HGF/c-Met pathway in these cancers.
Main Methods:
- Literature review of preclinical studies and clinical trials.
- Analysis of data on HGF/c-Met pathway inhibitors, including crizotinib.
Main Results:
- The HGF/c-Met pathway is a significant driver of gastrointestinal cancer proliferation, progression, and metastasis.
- Targeting HGF/c-Met, exemplified by crizotinib (a dual c-Met/ALK inhibitor), has demonstrated therapeutic potential, with crizotinib approved for ALK-rearranged lung cancers.
Conclusions:
- While targeting the HGF/c-Met pathway shows promise for gastrointestinal cancers, its precise antitumor mechanisms and resistance pathways require further elucidation.
- Future research should focus on identifying patient subgroups who will benefit most from therapy and exploring combination strategies to enhance efficacy and overcome resistance.
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