Molecular markers for gastric adenocarcinoma: an update

Abstract

Gastric cancer is the second most common cancer worldwide. Treatment of localized gastric cancer relies primarily on surgical intervention, although growing evidence suggests that the addition of chemoradiation may improve disease-free intervals and overall survival. In this regard, the current high rates of recurrence and subsequent poor survival have prompted an ever-increasing use of multimodal strategies, even for early-stage disease. However, these therapies are often limited by debilitating toxicities and varying degrees of response efficacy. As a result, pharmacogenomics, the study of specific genetic and molecular signatures that may be predictive of treatment outcomes, has gained considerable interest. For example, studies have demonstrated that the expression of enzymes involved in the metabolism or conjugation of commonly used chemotherapy agents, such as fluoropyrimidines and cisplatin, can serve as surrogate markers predictive of chemotherapy response. Polymorphisms in the genes encoding these enzymes have also been identified and may further account for altered expression patterns, resulting in varied clinical responses. Future work is necessary to further refine the list of molecular genetic markers and to identify novel markers for prognostic and predictive purposes. Technologies such as microarray analysis may be useful in identifying new molecular genetic markers, and further work may determine whether these markers can be employed to help stratify patients into different multimodal treatment regimens.