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Gastric adenocarcinoma

Abstract

Gastric cancers, with gastric adenocarcinoma (GAC) as the most common histological type, impose a considerable global health burden. Although the screening strategies for early detection have been shown to be successful in Japan and South Korea, they are either not implemented or not feasible in most of the world, leading to late diagnosis in most patients. Helicobacter pylori infection contributes to the development of many endemic GACs, and pre-emptive eradication or early treatment of this bacterial infection might provide effective primary prevention. GACs are phenotypically and genotypically heterogeneous. Localized (clinical stage I) GAC is best treated either endoscopically or with limited surgical resection, but clinical stage II or stage III tumours require multidisciplinary adjunctive approaches in addition to surgery. Although GAC is highly treatable in its early stages, advanced (clinical stage IV) GAC has a median survival of just 9–10 months. However, detailed molecular and immune profiling of GAC is yielding promise; early studies with immune checkpoint inhibitors suggest that GAC is amenable to immune modulation. Molecular studies have yielded a vast quantity of new information for potential exploitation. Nevertheless, advances against GACs have lagged compared with other tumours of similar incidence, and more research is necessary to overcome the obstacles to prolong survival.

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Figure 1: Global incidence of gastric adenocarcinoma in 2012.
Figure 2: The Siewert–Stein classification of gastroesophageal region cancers.
Figure 3: Helicobactor pylori exerts oncogenic effects on the gastric epithelium that can result in gastric adenocarcinoma.
Figure 4: Molecular classification of gastric adenocarcinoma.
Figure 5: Molecular alterations in receptor tyrosine kinases and TP53 and potential target therapy in gastric adenocarcinoma.
Figure 6: Molecular alterations common in gastric adenocarcinoma.
Figure 7: Adaptive T cell response controlled by co-stimulatory and co-inhibitory signalling in the tumour microenvironment.
Figure 8: Histological classification of gastric adenocarcinoma.
Figure 9: A representative treatment algorithm for gastric adenocarcinoma.

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Introduction (J.A.A.); Epidemiology (D.F.); Mechanisms/pathophysiology (S.S., D.F. and J.A.A.); Diagnosis, screening and prevention (T.S. and D.F.); Management (T.S., J.L. and Y.Y.J.); Quality of life (J.L. and J.A.A.); Outlook (J.A.A.); Overview of Primer (J.A.A.).

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Correspondence to Jaffer A. Ajani.

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Competing interests

J.A.A. has received research grants from Taiho Pharma, Genentech, Roche, Bristol-Myers Squibb, Takeda, Gilead, Merck USA, FivePrime, Lilly and DeltaFly Pharma, and honoraria from Taiho, Celgene, Bristol-Myers Squibb and Roche. Y.Y.J. has received research funding from Boehringer Ingelheim, Greentech, Bayer, Merk, Lilly, Pfizer and BristolMyers Squibb. All other authors declare no competing interests.

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Ajani, J., Lee, J., Sano, T. et al. Gastric adenocarcinoma. Nat Rev Dis Primers 3, 17036 (2017). https://doi.org/10.1038/nrdp.2017.36

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