Molecular classification of gastric cancer: Towards a pathway-driven targeted therapy.
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.
Department of Pathology, School of Medicine, Universidad de La Frontera, CEGIN-BIOREN, Temuco, Chile.
Ismael
I
Riquelme
Department of Pathology, School of Medicine, Universidad de La Frontera, CEGIN-BIOREN, Temuco, Chile.
Kathleen
K
Saavedra
Department of Pathology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.|UC-Center for Investigational Oncology (CITO), Pontificia Universidad Católica de Chile, Santiago, Chile.
Jaime A
JA
Espinoza
Department of Pathology, School of Medicine, Universidad de La Frontera, CEGIN-BIOREN, Temuco, Chile.
Helga
H
Weber
Department of Pathology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.|UC-Center for Investigational Oncology (CITO), Pontificia Universidad Católica de Chile, Santiago, Chile.
Patricia
P
García
UC-Center for Investigational Oncology (CITO), Pontificia Universidad Católica de Chile, Santiago, Chile.|Department of Hematology Oncology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.|Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, Chile.
Bruno
B
Nervi
UC-Center for Investigational Oncology (CITO), Pontificia Universidad Católica de Chile, Santiago, Chile.|Department of Hematology Oncology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
Marcelo
M
Garrido
UC-Center for Investigational Oncology (CITO), Pontificia Universidad Católica de Chile, Santiago, Chile.|Department of Hematology Oncology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.|Advanced Center for Chronic Diseases (ACCDIS), Pontificia Universidad Católica de Chile, Santiago, Chile.
Alejandro H
AH
Corvalán
Department of Pathology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.|UC-Center for Investigational Oncology (CITO), Pontificia Universidad Católica de Chile, Santiago, Chile.|Advanced Center for Chronic Diseases (ACCDIS), Pontificia Universidad Católica de Chile, Santiago, Chile.
Juan Carlos
JC
Roa
Department of Pathology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.|UC-Center for Investigational Oncology (CITO), Pontificia Universidad Católica de Chile, Santiago, Chile.
Carolina
C
Bizama
D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods* / Q000639:trends; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000145:classification / Q000188:drug therapy* / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019859:Proto-Oncogene Proteins c-met; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human
cancer stem cells; chemotherapy; gastric cancer; molecular classification; signaling pathway