Molecular classification of gastric cancer: Towards a pathway-driven targeted therapy

Ismael Riquelme, Kathleen Saavedra, Jaime A. Espinoza, Helga Weber, Patricia García, Bruno Nervi, Marcelo Garrido, Alejandro H. Corvalán, Juan Carlos Roa and Carolina Bizama _

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Oncotarget. 2015; 6:24750-24779. https://doi.org/10.18632/oncotarget.4990

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Ismael Riquelme1,*, Kathleen Saavedra1,*, Jaime A. Espinoza2,3, Helga Weber1, Patricia García2,3, Bruno Nervi3,4,5, Marcelo Garrido3,4, Alejandro H. Corvalán3,4,6, Juan Carlos Roa2,3,6 and Carolina Bizama2,3

1 Department of Pathology, School of Medicine, Universidad de La Frontera, CEGIN-BIOREN, Temuco, Chile

2 Department of Pathology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile

3 UC-Center for Investigational Oncology (CITO), Pontificia Universidad Católica de Chile, Santiago, Chile

4 Department of Hematology Oncology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile

5 Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, Chile

6 Advanced Center for Chronic Diseases (ACCDIS), Pontificia Universidad Católica de Chile, Santiago, Chile

* These authors contributed equally to this work

Correspondence to:

Carolina Bizama, email:

Juan Carlos Roa, email:

Keywords: gastric cancer, chemotherapy, molecular classification, signaling pathway, cancer stem cells

Received: April 16, 2015 Accepted: July 17, 2015 Published: July 22, 2015


Gastric cancer (GC) is the third leading cause of cancer mortality worldwide. Although surgical resection is a potentially curative approach for localized cases of GC, most cases of GC are diagnosed in an advanced, non-curable stage and the response to traditional chemotherapy is limited. Fortunately, recent advances in our understanding of the molecular mechanisms that mediate GC hold great promise for the development of more effective treatment strategies. In this review, an overview of the morphological classification, current treatment approaches, and molecular alterations that have been characterized for GC are provided. In particular, the most recent molecular classification of GC and alterations identified in relevant signaling pathways, including ErbB, VEGF, PI3K/AKT/mTOR, and HGF/ MET signaling pathways, are described, as well as inhibitors of these pathways. An overview of the completed and active clinical trials related to these signaling pathways are also summarized. Finally, insights regarding emerging stem cell pathways are described, and may provide additional novel markers for the development of therapeutic agents against GC. The development of more effective agents and the identification of biomarkers that can be used for the diagnosis, prognosis, and individualized therapy for GC patients, have the potential to improve the efficacy, safety, and cost-effectiveness for GC treatments.

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