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Abstract
The better understanding of the molecular mechanisms behind gastric cancer has led to the development of new therapeutic strategies that are likely to improve patient outcomes in the near future. Recently, targeting the HER2 and the VEGF pathways with trastuzumab and ramucirumab, respectively, have been found to improve survival, while directed therapies against a number of other pathways are under clinical evaluation. These include the hepatocyte growth factor and its receptor c-MET, the insulin-like growth factor 1, the fibroblast growth factor, the mammalian target of rapamycin (mTOR), the epidermal growth factor receptor, and other pathways, as well as relevant immunotherapeutic strategies. This article reviews recent advances and future trends of these concepts for gastric cancer and adenocarcinoma of the gastroesophageal junction.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Key issues
Gastric cancer is the second most frequent cause of cancer-related death worldwide.
Despite recent advances in chemotherapy, median overall survival in patients with gastric cancer is still 1 year.
The better understanding of the molecular mechanisms behind gastric cancer has led to the development of new therapeutic strategies that may improve patient‘s outcome in the future.
Recently, targeting the HER2 and the VEGF pathways with trastuzumab and ramucirumab, respectively, have been shown to improve survival. This will change the way in which we stage and treat this disease in the near future.
EGFR antibodies failed to show any beneficial effects and are less likely to play a therapeutic role in gastric cancer.
Targeting mTOR with everolimus, VEGF-A with bevacizumab and matrix metalloproteinases with marimastat has shown some activity in clinical trials but failed to improve overall survival as the primary endpoint.
New compounds against HER2 such as trastuzumab emtansine and pertuzumab as well as HGF/mesenchymal epithelial transition factor antibodies are in Phase III trials for metastatic disease. Other targeted therapies against a number of molecular pathways as well as immunotherapy are under early clinical evaluation.