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  • Review Article
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Gastric cancer—molecular and clinical dimensions

Nature Reviews Clinical Oncology volume 10, pages 643–655 (2013)Cite this article

Subjects

Key Points

  • Globally, gastric cancer is the fourth most common cancer in men and fifth most common cancer in women

  • Helicobacter pylori is the most intriguing and best studied risk factor for sporadic gastric cancers

  • Signalling pathways and cancer stem cells have key roles in carcinogenesis and progression

  • Localized gastric cancer can be cured by primary surgery, but adjunctive therapies increase the cure rate

  • New somatic genes altered in gastric cancer (such as ARID1A, FAT4, MLL and KMT2C) have been identified, but thorough interrogation of gastric cancer is as yet incomplete

  • Therapeutic approaches that exploit the capabilities of the host immune mechanisms hold immense promise

Abstract

Gastric cancer imposes a considerable health burden around the globe despite its declining incidence. The disease is often diagnosed in advanced stages and is associated with a poor prognosis for patients. An in-depth understanding of the molecular underpinnings of gastric cancer has lagged behind many other cancers of similar incidence and morbidity, owing to our limited knowledge of germline susceptibility traits for risk and somatic drivers of progression (to identify novel therapeutic targets). A few germline (PLCE1) and somatic (ERBB2, ERBB3, PTEN, PI3K/AKT/mTOR, FGF, TP53, CDH1 and MET) alterations are emerging and some are being pursued clinically. Novel somatic gene targets (ARID1A, FAT4, MLL and KMT2C) have also been identified and are of interest. Variations in the therapeutic approaches dependent on geographical region are evident for localized gastric cancer—differences that are driven by preferences for the adjuvant strategies and the extent of surgery coupled with philosophical divides. However, greater uniformity in approach has been noted in the metastatic cancer setting, an incurable condition. Having realized only modest successes, momentum is building for carrying out more phase III comparative trials, with some using biomarker-based patient selection strategies. Overall, rapid progress in biotechnology is improving our molecular understanding and can help with new drug discovery. The future prospects are excellent for defining biomarker-based subsets of patients and application of specific therapeutics. However, many challenges remain to be tackled. Here, we review representative molecular and clinical dimensions of gastric cancer.

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Figure 1: Molecular carcinogenesis of Helicobacter pylori in gastric cancer.
Figure 2: microRNA targets and functions in gastric cancer.
Figure 3: Targeted therapy in gastric cancer.

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Acknowledgements

The authors are supported by grants from the Caporella, Cantu, Smith, Park, Fairman, Frazier, Sultan, Oaks, Vansteklenberg and Milrod families, by the Kevin Fund, Schecter Private Fund and the Rivercreek Foundation and a Multidisciplinary Research Grant from University of Texas MD Anderson Cancer Center. J. A. Ajani is also supported by grants RO1CA138671 and ROaCA172741 awarded by the National Cancer Institute, Bethesda, MD, USA. The authors also thank the editorial staff of Nature Reviews Clinical Oncology for their editorial assistance in considerably improving the clarity and organization of the manuscript.

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  1. Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard (FC10.3022), Houston, 77030, TX, USA

    Roopma Wadhwa, Shumei Song, Yixin Yao & Jaffer A. Ajani

  2. Department of Systems Biology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard (FC10.3022), Houston, 77030, TX, USA

    Ju-Seog Lee

  3. Department of Epidemiology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard (FC10.3022), Houston, 77030, TX, USA

    Qingyi Wei

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Wadhwa, R., Song, S., Lee, JS. et al. Gastric cancer—molecular and clinical dimensions. Nat Rev Clin Oncol 10, 643–655 (2013). https://doi.org/10.1038/nrclinonc.2013.170

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