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World J Gastrointest Oncol. May 15, 2017; 9(5): 194-208
Published online May 15, 2017. doi: 10.4251/wjgo.v9.i5.194
Molecular classifications of gastric cancers: Novel insights and possible future applications
Silvio Ken Garattini, Debora Basile, Monica Cattaneo, Valentina Fanotto, Elena Ongaro, Marta Bonotto, Francesca V Negri, Rosa Berenato, Paola Ermacora, Giovanni Gerardo Cardellino, Mariella Giovannoni, Nicoletta Pella, Mario Scartozzi, Lorenzo Antonuzzo, Nicola Silvestris, Gianpiero Fasola, Giuseppe Aprile
Silvio Ken Garattini, Debora Basile, Monica Cattaneo, Valentina Fanotto, Elena Ongaro, Marta Bonotto, Paola Ermacora, Giovanni Gerardo Cardellino, Mariella Giovannoni, Nicoletta Pella, Gianpiero Fasola, Giuseppe Aprile, Department of Oncology, University and General Hospital, 33100 Udine, Italy
Francesca V Negri, Medical Oncology, University Hospital, 43126 Parma, Italy
Rosa Berenato, Medical Oncology, National Cancer Institute, IRCCS, 20133 Milano, Italy
Mario Scartozzi, Department of Oncology, University Hospital, 09124 Cagliari, Italy
Lorenzo Antonuzzo, Department of Oncology, University and General Hospital, 50134 Firenze, Italy
Nicola Silvestris, Medical Oncology, National Cancer Institute, IRCCS, 70124 Bari, Italy
Author contributions: Garattini SK designed the general profile and the aims of the paper; Basile D, Cattaneo M, Fanotto V, Ongaro E, Bonotto M, Ermacora P, Cardellino GG, Giovannoni M and Pella N did the literature review and contributed to the writing of specific paragraphs; Negri FV, Berenato R, Scartozzi M, Antonuzzo L, Silvestris N and Fasola G provided specific expert opinions on the topics; Aprile G critically reviewed the draft and supervised the writing of the paper.
Conflict-of-interest statement: The authors have no conflict of interest to disclose.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Giuseppe Aprile, MD, Department of Oncology, University and General Hospital, Via Pozzuolo 330, 33100 Udine, Italy. giuseppe.aprile@asuiud.sanita.fvg.it
Telephone: +39-0432-555308 Fax: +39-0432-552751
Received: August 27, 2016
Peer-review started: August 27, 2016
First decision: November 21, 2016
Revised: February 28, 2017
Accepted: March 14, 2017
Article in press: March 17, 2017
Published online: May 15, 2017
Processing time: 257 Days and 21.2 Hours
Abstract

Despite some notable advances in the systemic management of gastric cancer (GC), the prognosis of patients with advanced disease remains overall poor and their chance of cure is anecdotic. In a molecularly selected population, a median overall survival of 13.8 mo has been reached with the use of human epidermal growth factor 2 (HER2) inhibitors in combination with chemotherapy, which has soon after become the standard of care for patients with HER2-overexpressing GC. Moreover, oncologists have recognized the clinical utility of conceiving cancers as a collection of different molecularly-driven entities rather than a single disease. Several molecular drivers have been identified as having crucial roles in other tumors and new molecular classifications have been recently proposed for gastric cancer as well. Not only these classifications allow the identification of different tumor subtypes with unique features, but also they serve as springboard for the development of different therapeutic strategies. Hopefully, the application of standard systemic chemotherapy, specific targeted agents, immunotherapy or even surgery in specific cancer subgroups will help maximizing treatment outcomes and will avoid treating patients with minimal chance to respond, therefore diluting the average benefit. In this review, we aim at elucidating the aspects of GC molecular subtypes, and the possible future applications of such molecular analyses.

Keywords: Molecular biology; Immunotherapy; Gastric cancer; Classification; Targeted therapy

Core tip: TCGA individuates four molecular subtypes: Chromosomal instability, microsatellite instability, genomically stable and Epstein-Barr virus positive tumors. Asian Cancer Research Group classification partially overlaps with the previous one. Although not prospectively validated, these novel classifications suggest that different subtypes of gastric cancer might be treated with specific therapeutic strategies in the near future.