Personalized medicine in gastric cancer: Where are we and where are we going?

Abstract

Despite improvements in adjuvant therapies for gastric cancer in recent years, the disease is characterized by high recurrence rates and a dismal prognosis. The major improvement in the treatment of recurrent or metastatic gastric cancer in recent years has been the incorporation of trastuzumab, a monoclonal antibody that inhibits human epidermal growth factor receptor 2 (HER2) heterodimerization, after the demonstrated predictive value of the overexpression and/or amplification of this receptor. Beyond HER2, other genetic abnormalities have been identified, and these mutations may be targetable by tyrosine kinase inhibitors or monoclonal antibodies. The demonstration of four distinct molecular subtypes of gastric cancer by the Cancer Genome Atlas study highlight the enormous heterogeneity of the disease and its complex interplay between genetic and epigenetic alterations and provide a roadmap to implement genome-guided personalized therapy in gastric cancer. In the present review, we aim to discuss, from a clinical point of view, the genomic landscape of gastric cancer described in recent studies, the therapeutic insights derived from these findings, and the clinical trials that have been conducted and those in progress that take into account tailored therapies for gastric cancer.

RETRACTED ARTICLE: Decreased expression of miR-939 contributes to chemoresistance and metastasis of gastric cancer via dysregulation of SLC34A2 and Raf/MEK/ERK pathway

“…Although tremendous progress has been made in therapeutic strategies, the prognosis for GC patients using existing treatments remains unsatisfactory. The development of chemoresistance and metastasis are the leading causes of death for GC patients, however, the molecular mechanisms involved remain unclear [3–5]. Therefore, a better understanding of these molecular events will undoubtedly facilitate our ability to the development of novel therapeutic targets and strategies for GC treatment.…”

LEM domain containing 1 promotes proliferation via activating the PI3K/Akt signaling pathway in gastric cancer

“…In recent years, increased understanding of clinical features of GC has promoted advances in diagnosis and treatments for GC. Although there have been several genes that have been functionally characterized in GC, the analysis of genetic expression patterns in human GC remains insufficient to be perfectly applied to clinical diagnosis and treatments …”

Genetic and histological subtypes of gastric cancer reviewed, particularly emphasising on microsatellite instability and E-cadherin gene mutation

“…Each subtype was found throughout the stomach, but CIN tumours rates were higher in the gastroesophageal junction/cardia, whereas most EBV-positive tumours occurred in the gastric fundus or body [9]. Genomically stable tumours were diagnosed at an earlier age, whereas MSI tumours were diagnosed at relatively older ages [7]. MSI patients tended to be female, but most EBV-positive GCs were observed in males [2].…”

“…Most of GCs are sporadic tumours where genetic alterations are frequently reported. Nevertheless, no major high-penetrance genes have yet been discovered [5], although genetic factors might play an important role in gastric carcinogenesis by possibly affecting immune and inflammatory responses, especially in cases of the bacterium Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV) infections and thereby altering the susceptibility to gastric cancer [6][7][8]. GCs classified molecularly by the Cancer Genome Atlas (TCGA) categorises GC into four subtypes: tumours positive for the EBV virus (9%), tumours with microsatellite instability (22%), genomically stable tumours (20%) and tumours with chromosomal instability (CIN) at 50% [9].…”

“…The vast majority of GCs are adenocarcinomas, which can be further subdivided into intestinal and diffuse subtypes according to the Lauren classification published in 1965 [4,7,15] (Fig. 1).…”