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Page 6 of 9                                    Eto et al. J Cancer Metastasis Treat 2018;4:23  I  http://dx.doi.org/10.20517/2394-4722.2017.73

               safety profile of nivolumab in patients with advanced GC or GEJ cancer was manageable and similar to
               that reported in patients with other advanced solid tumors. Based on these results, the Japanese Ministry of
               Health, Labor and Welfare approved nivolumab for the treatment of unresectable advanced or recurrent GC
               which has progressed after chemotherapy. Currently, trials are ongoing to evaluate the efficacy of immune
               checkpoint inhibitors in earlier lines of GC treatment.


               Ongoing trials in Japan
               The RAINFALL trial is ongoing to evaluate the effectiveness of ramucirumab in combination with Cape/
               CDDP compared to Cape/CDDP alone as first-line treatment of metastatic GC or GEJ adenocarcinoma
               (NCT02314117). The SOLAR trial, a phase III trial comparing TAS-118 (S-1 plus leucovorin) and oxaliplatin
               vs. SP as first-line treatment, is recruiting patients with advanced GC in Japan and Korea (NCT02322593).

               Precision medicine for GC
               Treatment of cancer is likely to shift and be tailored towards personalized therapy based on detailed molecular
               information, known as precision medicine. The Cancer Genome Atlas Research Network reported the results
               of molecular classification of GC through integrative genomic analysis, which suggested that GC could be
               divided into four subtypes : (1) Epstein-Barr virus-related tumors; (2) microsatellite instability represented
                                     [47]
               as elevated mutation rates and MLH1 silencing; (3) genomically stable tumors that are strongly related with
               diffuse histology, RHOA mutations, and CLDN18-ARHGAP fusion; and (4) chromosomal instability that
               mainly comprises intestinal histology, TP53 mutation, and focal amplification of the receptor tyrosine
               kinase. Another study reported that GC can be classified into four subtypes : (1) microsatellite unstable;
                                                                                [48]
               (2) microsatellite stable (MSS) with TP53 mutation; (3) MSS without TP53 mutation; and (4) MSS with
               epithelial-to-mesenchymal transition (EMT). This study found that the MSS/EMT subtype was related
               to poor prognosis. Further analysis is needed to establish genome-based precision medicine.



               CONCLUSION
               The main goal of treatment for metastatic GC patients is to prolong patient survival while preserving
               quality of life. In addition to the combination of conventional cytotoxic drugs, several newly developed
               agents, including targeted molecules and immune checkpoint inhibitors, have shown favorable results in
               the treatment of metastatic GC. Efforts should be focused on achieving precision medicine based on the
               molecular information of GC.



               DECLARATIONS
               Authors’ contributions
               Concept, design, literature search, and manuscript preparation: Eto K
               Manuscript editing: Ida S
               Design, manuscript editing, and manuscript review: Watanabe M
               Manuscript review: Baba H


               Financial support and sponsorship
               None.


               Conflicts of interest
               Authors declare that they have no conflicts of interest.


               Patient consent
               Not applicable.
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