Molecular biology of gastric cancer

Abstract

Despite its decreasing incidence overall, gastric cancer is still a challenging disease. Therapy is based mainly upon surgical resection when the tumour remains localised in the stomach. Conventional chemotherapy may play a role in treating micrometastatic disease and is effective as palliative therapy for recurrent or advanced disease. However, the knowledge of molecular pathways implicated in gastric cancer pathogenesis is still in its infancy and the contribution of molecular biology to the development of new targeted therapies in gastric cancer is far behind other more common cancers such as breast, colon or lung. This review will focus first on the difference of two well defined types of gastric cancer: intestinal and diffuse. A discussion of the cell of origin of gastric cancer with some intriguing data implicating bone marrow derived cells will follow, and a comprehensive review of different genetic alterations detected in gastric cancer, underlining those that may have clinical, therapeutic or prognostic implications.

MCM-2 and MCM-5 Expression in Gastric Adenocarcinoma: Clinical Significance and Comparison with Ki-67 Proliferative Marker

“…Moreover, it should be noted that the two different types of gastric cancer, defined as diffuse-and intestinal-type are considered to be characterized by distinct behavior and genetics [34][35][36]. Multiple genetic and epigenetic alterations in oncogenes, tumor-suppressor genes, cell cycle regulators, cell adhesion molecules, DNA repair-related genes and genetic instability, as well as telomerase activation are implicated in the multi-step process of human gastric neoplasia [34][35][36].…”

“…Multiple genetic and epigenetic alterations in oncogenes, tumor-suppressor genes, cell cycle regulators, cell adhesion molecules, DNA repair-related genes and genetic instability, as well as telomerase activation are implicated in the multi-step process of human gastric neoplasia [34][35][36]. However, particular combinations of these alterations differ in the two histological types of gastric cancer, indicating that intestinal and diffuse carcinomas present distinct tumorogenic pathways [34][35][36]. In this context, we further analyzed separately diffuse-and intestinal-type gastric adenocarcinoma cases.…”

Prognostic value of miR-141 downregulation in gastric cancer

“…There is regional variation in worldwide incidence rates, with more than 70% of gastric cancers occurring in developing countries because of high prevalence of Helicobacter pylori (Wang et al, 2002). Even with maximal trimodality therapies, the prognosis of gastric cancer patients remains poor, with a 5-year survival rate of 25-35% for loco-regional disease and a median survival rate ranging from 10 to 14 months in advanced disease states (Cervantes et al, 2007). Therefore, it is important to identify novel markers and therapeutic targets for an improvement in the prognosis and mortality of gastric cancer.…”

The overexpression of c-met as a prognostic indicator for gastric carcinoma compared to p53 and p21 nuclear accumulation

“…Further characterization of the various molecular genetic pathways should elucidate the role of independent prognostic factors and afford opportunities to discriminate subgroups with different biological behaviour (20). More specific and effective therapies could be developed according to the tumor characterization with regard to independent molecular prognostic factors (2).…”