MET-targeted therapy for gastric cancer: the importance of a biomarker-based strategy

Abstract The MET protooncogene encodes the receptor tyrosine kinase c-MET (MET). Aberrant activation of MET signaling occurs in a subset of advanced malignancies, including gastric cancer, and promotes tumor cell growth, survival, migration, and invasion as well as tumor angiogenesis, suggesting its potential importance as a therapeutic target. MET can be activated by two distinct pathways that are dependent on or independent of its ligand, hepatocyte growth factor (HGF), with the latter pathway having been attributed mostly to MET amplification in gastric cancer. Preclinical evidence has suggested that interruption of the HGF–MET axis either with antibodies to HGF or with MET tyrosine kinase inhibitors (TKIs) has antitumor effects in gastric cancer cells. Overexpression of MET occurs frequently in gastric cancer and has been proposed as a potential predictive biomarker for anti-MET therapy. However, several factors can trigger such MET upregulation in a manner independent of HGF, suggesting that gastric tumors with MET overexpression are not necessarily MET driven. On the other hand, gastric cancer cells with MET amplification are dependent on MET signaling for their survival and are thus vulnerable to MET TKI treatment. Given the low prevalence of MET amplification in gastric cancer (approximately 8 %), testing for this genetic change would substantially narrow the target population but it might constitute a better biomarker than MET overexpression for M...
Source: Gastric Cancer - Category: Gastroenterology Source Type: research

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ConclusionOur study demonstrates that up-regulated NID2 plays an important role in promoting the invasion and migration of GC cells and has a potential of being a novel biomarker for diagnosis, treatment and prognosis of GC in the future.
Source: Pathology Research and Practice - Category: Pathology Source Type: research
Authors: Simondurairaj C, Krishnakumar R, Sundaram S, Venkatraman G Abstract The aim of the study is to analyse the expression of Interleukin-6 receptor in different human gastric tissue and to correlate with the clinicopathological features of the patients. Immunohistochemistry was done against the IL-6R antibody and the Q-score was calculated from the staining pattern. Higher Q-scores were observed in tumour cells than the adjacent normal cells which were statistically significant. We also observed a significant correlation between the expressions of IL-6R and the clinicopathological features These findings sugge...
Source: Cancer Investigation - Category: Cancer & Oncology Tags: Cancer Invest Source Type: research
TUESDAY, July 23, 2019 -- Type 2 diabetes mellitus increases the risk for gastric cancer after treatment for Helicobacter pylori infection, according to a study published online July 11 in Diabetes Care. Ka Shing Cheung, M.B.B.S., M.P.H., from The...
Source: Drugs.com - Pharma News - Category: Pharmaceuticals Source Type: news
Authors: Quach DT, Hiyama T Abstract The assessment of endoscopic gastric atrophy (EGA) according to the Kimura-Takemoto classification has been reported to correlate well with histological assessment. Although agreement among beginner endoscopists was less than that among experienced endoscopists, it has been shown that agreement level could markedly improve and remained stable after proper training. Several cohort studies have consistently shown that the severity of EGA at baseline is significantly associated with the presence of advanced precancerous gastric lesions and gastric cancer, as well as the development...
Source: Clinical Endoscopy - Category: Gastroenterology Tags: Clin Endosc Source Type: research
This study investigates the role of LAMC2 in epithelial-mesenchymal transition (EMT) and angiogenesis in CCA and explores the underlying mechanism(s) . Differentially expressed genes related to CCA were initially screened using a microarray analysis, and the interaction between LAMC2 and the EGFR signaling pathway was identified.
Source: American Journal of Pathology - Category: Pathology Authors: Tags: Regular article Source Type: research
This study aimed at evaluating DOP efficiency at inhibiting 1-Methyl-2-nitro-1-nitrosoguanidine (MNNG) induced precancerous lesions of gastric cancer (PLGC) in rats through the Wnt/b-catenin pathway and analyzing the variations of serum endogenous metabolites. PLGC was established in male Sprague-Dawley (SD) rats by administering 150 μg/mL MNNG in drinking water for 7 months and giving 0.1 mL of 10% NaCl once weekly during the initial 20 weeks. Treatment with DOP inhibited the progress of PLGC through decreasing the expression of β-catenin by immunohistochemical analysis. The futher study indicated DOP down...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
Conditions:   Gastric Cancer Stage;   CT;   MRI;   Neoadjuvant Therapy Intervention:   Other: No intervention Sponsor:   Henan Cancer Hospital Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Source: OncoTargets and Therapy - Category: Cancer & Oncology Tags: OncoTargets and Therapy Source Type: research
Source: Cancer Management and Research - Category: Cancer & Oncology Tags: Cancer Management and Research Source Type: research
ConclusionsOur CNN system showed high accuracy, sensitivity and specificity in the diagnosis of early gastric cancer. It is anticipated that more progress will be made in optimization of the CNN diagnostic system and further development of artificial intelligence in the medical field.
Source: Gastric Cancer - Category: Gastroenterology Source Type: research
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