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Recent advances in the molecular diagnostics of gastric cancer.

ABSTRACT: Gastric cancer (GC) is the third most common cause of cancer-related death in the world, representing a major global health issue. Although the incidence of GC is declining, the outcomes for GC patients remain dismal because of the lack of effective biomarkers to detect early GC and predict both recurrence and chemosensitivity. Current tumor markers for GC, including serum carcinoembryonic antigen and carbohydrate antigen 19-9, are not ideal due to their relatively low sensitivity and specificity. Recent improvements in molecular techniques are better able to identify aberrant expression of GC-related molecules, including oncogenes, tumor suppressor genes, microRNAs and long non-coding RNAs, and DNA methylation, as novel molecular markers, although the molecular pathogenesis of GC is complicated by tumor heterogeneity. Detection of genetic and epigenetic alterations from gastric tissue or blood samples has diagnostic value in the management of GC. There are high expectations for molecular markers that can be used as new screening tools for early detection of GC as well as for patient stratification towards personalized treatment of GC through prediction of prognosis and drug-sensitivity. In this review, the studies of potential molecular biomarkers for GC that have been reported in the publicly available literature between 2012 and 2015 are reviewed and summarized, and certain highlighted papers are examined.

SUBMITTER: Kanda M

PROVIDER: S-EPMC4566379 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Recent advances in the molecular diagnostics of gastric cancer.

Kanda Mitsuro M Kodera Yasuhiro Y

World journal of gastroenterology 20150901 34

Gastric cancer (GC) is the third most common cause of cancer-related death in the world, representing a major global health issue. Although the incidence of GC is declining, the outcomes for GC patients remain dismal because of the lack of effective biomarkers to detect early GC and predict both recurrence and chemosensitivity. Current tumor markers for GC, including serum carcinoembryonic antigen and carbohydrate antigen 19-9, are not ideal due to their relatively low sensitivity and specificit ...[more]

PMID: 26379391

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Project description:Gastric cancer (GC) is the fifth most common cancer worldwide. Despite recent improvements in treatment quality and options, advanced gastric cancer remains one of the hardest to cure cancers, with a median overall survival (OS) of 10-12 months and a 5-year OS of approximately 5-20%. There is an unmet need for further efforts to palliate disease-related symptoms, improve quality of life, increase tumor response rate, and prolong progression free and overall survival while balancing the toxicities of therapy. The most common type of GC is adenocarcinoma, which demonstrates morphological, biological, and clinical heterogeneity. A plethora of genomic alterations and the activation of numerous molecular pathways including human epidermal growth receptor 2 (HER2), epidermal growth factor receptor (EGFR), fibroblast growth factor receptor-2 (FGFR2), mesenchymal epidermal transforming factor receptor (MET), and the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) are responsible for the complex heterogeneity of GC. Efforts to validate the therapeutic effects of inhibiting some of these aberrantly expressed pathways have failed to lead to a clinically meaningful outcome apart from the overexpression/amplification of the HER2 gene, inhibition of which has had a significant impact on clinical practice. The only available biomarkers to guide the effective treatment of patients with advanced GC are HER2 overexpression, MSI/PD-L1 status, and FGFR alterations. Various anti-HER2 agents have been evaluated after the success of the ToGA trial, but none led to a significant enough clinical improvement to be considered a viable alternative for HER2-targeted therapy in advanced GC until the global Keynote-811 trial, which added pembrolizumab to trastuzumab in combination with chemotherapy. This combination demonstrated a survival advantage for the first time in the 11 years since ToGA. Trastuzumab deruxtecan (T-DXd) was also found to be effective in patients who had already received >2 previous lines of treatment. Despite these promising avenues, the optimal management of HER-2 positive GC still requires further development.

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Recent advances in the molecular diagnostics of gastric cancer.

Publications

Recent advances in the molecular diagnostics of gastric cancer.

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