Minireviews
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 14, 2019; 25(38): 5773-5788
Published online Oct 14, 2019. doi: 10.3748/wjg.v25.i38.5773
Targeted therapies in metastatic gastric cancer: Current knowledge and future perspectives
Antonio Pellino, Erika Riello, Floriana Nappo, Stefano Brignola, Sabina Murgioni, Selma Ahcene Djaballah, Sara Lonardi, Vittorina Zagonel, Massimo Rugge, Fotios Loupakis, Matteo Fassan
Antonio Pellino, Erika Riello, Floriana Nappo, Sabina Murgioni, Selma Ahcene Djaballah, Sara Lonardi, Vittorina Zagonel, Fotios Loupakis, Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua 35100, Italy
Antonio Pellino, Floriana Nappo, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua 35100, Italy
Erika Riello, Stefano Brignola, Massimo Rugge, Matteo Fassan, Surgical Pathology & Cytopathology Unit, Department of Medicine, University of Padua, Padua 35100, Italy
Massimo Rugge, Veneto Cancer Registry, Padua 35100, Italy
Author contributions: Pellino A, Riello and Nappo F wrote the manuscript; Brignola S, Murgioni S, Ahcene Djaballah S, Lonardi S, Zagonel V and Rugge M contributed to the writing of the manuscript; Loupakis L and Fassan M equally contributed as senior authors, designed the aim of the editorial and wrote the manuscript.
Conflict-of-interest statement: Fotios Loupakis had roles as consultant or advisor for Roche, Bayer, Amgen and Genentech. Sara Lonardi had roles as consultant or advisor for Amgen, Bayer, Merck Serono, Lilly; she received research funding from Amgen, Merck Serono and she is part of speakers bureau of Lilly, BMS. Vittorina Zagonel received honoraria and had roles as consultant or advisor for Bristol-Mayers Squibb, Bayer, Roche, Pfizer, Janssen, Novartis, Astellas, Servier; he had roles as consultant or advisor for Celgene, Merck. Matteo Fassan received research funding from Astellas Pharma. All the others authors declare no conflict of interest regarding the publication of this article.
Open-Access: This article is an open-access article which was selected byan 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/
Corresponding author: Matteo Fassan, MD, PhD, Associate Professor, Oncologist, Veneto Institute of Oncology IOV-IRCCS, via Gattamelata 64, Padua 35100, Italy. fotios.loupakis@iov.veneto.it
Telephone: +39-49-8215919 Fax: +39-49-8217929
Received: July 15, 2019
Peer-review started: July 16, 2019
First decision: August 2, 2019
Revised: August 26, 2019
Accepted: September 27, 2019
Article in press: September 27, 2019
Published online: October 14, 2019
Abstract

Gastric cancer (GC) represents a leading cause of cancer related morbidity and mortality worldwide accounting for more than 1 million of newly diagnosed cases and thousands of deaths every year. In the last decade, the development of targeted therapies and the optimization of already available chemotherapeutic drugs has expanded the available treatment options for advanced GC and granted better survival expectations to the patients. At the same time, global efforts have been undertaken to investigate in detail the genomic and epigenomic heterogeneity of this disease, resulting in the identification of new specific and sensitive predictive and prognostic biomarkers and in innovative molecular classifications based on gene expression profiling. Nonetheless, several randomized studies aimed at exploring new innovative agents, such as immune checkpoint inhibitors, failed to demonstrate clinically meaningful survival advantages. Therefore, it is essential to further improve the molecular characterization of GC subgroups in order to provide researchers and medical oncologists with new tools for patients’ selection and stratification in future clinical development programs and subsequent trials. The aim of the present manuscript is to provide a global overview of the recent molecular classifications from The Cancer Genome Atlas and the Asian Cancer Research Group and to present key promising developments in the field of immunotherapy and targeted therapies in metastatic GC.

Keywords: Gastric cancer, Personalized medicine, Predictive biomarkers, Molecular diagnostic, The Cancer Genome Atlas, Asian Cancer Research Group

Core tip: Gastric cancer (GC) still represents a leading cause of cancer related morbidity and mortality worldwide accounting for more than 1 million of newly diagnosed cases and thousands of deaths every year. In the last decade, global efforts have been undertaken to investigate in detail the genomic and epigenomic heterogeneity of this disease, resulting in innovative molecular classifications of GC based on gene expression profiling and in the identification of new specific and sensitive predictive and prognostic biomarkers. At the same time, the development of targeted therapies has expanded the treatment scenario for advanced GC. The aim of the present manuscript is to provide a detailed and comprehensive overview of the recent molecular classifications from The Cancer Genome Atlas and the Asian Cancer Research Group and to present key promising developments in the field of immunotherapy and targeted therapies in metastatic GC.