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Page 8 of 12 Kamiya et al. J Cancer Metastasis Treat 2018;4:35 I http://dx.doi.org/10.20517/2394-4722.2017.76

overall response rates for bleeding, pain and obstruction symptoms were 74%, 67% and 68% respectively, low
[72]
biological equivalent dose of > 39 Gy regimens appear to be adequate for symptom palliation .

TARGETED THERAPIES
As in other solid organ tumors, the biological abnormalities triggering the development and progression of
gastric cancer are increasingly elucidated through ongoing research. These findings have potentially impor-
tant implications as investigators attempt to elucidate the key pathways driving the tumor in each individual
patient.

Overexpression of the HER2 gene, which is present in approximately 10%-20% of gastric cancers, is more
common in intestinal type than diffuse type gastric cancer and more common in EGJ cancer than distal
gastric cancer. Following the phase III ToGA trial, which demonstrated statistically significant improvement
in PFS and OS with the addition of trastuzumab to a cisplatin/5-FU doublet regimen, trastuzumab was li-
censed in Europe for use in HER-2 positive disease in combination with capecitabine or 5-FU and cisplatin
[11]
doublet . This regimen currently represents the standard of care for these palliative patients. Also, the large
phase III RAINBOW trial and REGARD trial, have shown the survival benefit of ramucirumab, a monoclo-
nal antibody VEGFR-2 antagonist, as second line in the palliative setting [73,74] . Moreover, nivolumab, a fully
human IgG4 monoclonal antibody inhibitor of programmed death-1, significantly improved the median
overall survival in patients with advanced gastric cancer, or gastro-esophageal junction cancer, who had been
[75]
previously treated with two or more chemotherapy regimens (ATTRACTION-2 trial) . Several studies target-
ing HER2, VEGF, EGFR, T-DM1 are currently ongoing with some potentially favorable results [76-80] . Further
developments in molecular subtyping of gastric cancer are likely to offer new possibilities in personalized
treatment of gastric cancer in the future [81-84] .

CONCLUSION
It is clear that the multimodal therapy encompassing both radical surgical treatment and perioperative CT/
CRT offers the best possibility to cure resectable gastric cancer. In Western countries, minimally invasive
approaches and D2 dissection have been successfully implemented at some high-volume centers. However,
these procedures are still not standardized in the whole population-based case-load of incident cases, due to
the low incidence of gastric cancer in Europe and other Western populations. Although the prospective clin-
ical trials performed have achieved clear improvements in the therapeutic outcomes and patients’ prognosis
in the last decades, an optimal treatment for advanced gastric cancer has not been established, given the still
poor overall survival. Recent advances in molecular tumor biology of adenocarcinoma of the stomach offer
us important clues about future tailoring of gastric cancer treatment. Furthermore the rapid developments in
sequencing techniques are likely to revolutionize our understanding of disease biology in the next decades. It
is very likely that a number of new biomarkers will provide completely new options for personalized therapy,
which may realize substantial therapeutic improvements, with excellent efficacy and tolerable adverse effects.

DECLARATIONS
Authors’ contributions
Designed the study, reviewed the literature, and wrote the manuscript: Kamiya S
Contributed to writing the manuscript, drafting, critical revision, editing, and final approval of the final ver-
sion: Nilsson M
Contributed to critical reversion of the manuscript and final approval of the final version: Rouvelas I, Lind-
blad M

Availability of data and materials
Not applicable.