Gastric cancer—molecular and clinical dimensions

Abstract

Gastric cancer (GC) imposes a significant health burden around the globe despite its declining incidence. GC is often diagnosed in advanced stages and carries a poor prognosis. In depth understanding of molecular underpinnings of GC has lagged behind many other cancers of its magnitude, as a result our knowledge base for identifying germline susceptibility traits for risk and somatic drivers of progression (to identify novel therapeutic targets) is limited. A few germline (PLCE1) and somatic (ERBB2, ERBB3, PTEN, PI3K/AKT/mTOR, FGF, TP53, CDH1, and c-MET) alterations are emerging and some are being pursued in the clinic. Novel somatic gene targets, Arid1a, FAT4, and MLL/MLL3 are of interest. Clinically, variations in the therapeutic approaches for localized GC are evident by geographic regions. These are driven by preferences for the adjunctive strategies and the extent of surgery coupled with philosophical divides. However, there is a greater uniformity in approaches to metastatic cancer, an incurable condition. Having realized only modest successes, the momentum is building for carrying out more phase 3 comparative trials and some are using biomarker-based patient selection. Overall, rapid progress in biotechnology is improving our molecular understanding and can help with new drug discovery. The future prospects are excellent for defining biomarker-based subsets of patients and application of specific therapeutics. However, many challenges remain to be tackled. Here we review representative molecular and clinical dimensions of GC.

Long Noncoding RNA GAPLINC Regulates CD44-Dependent Cell Invasiveness and Associates with Poor Prognosis of Gastric Cancer

“…Currently, most reported potential biomarkers for gastric cancer are protein-coding genes (PCG), including the novel somatic gene targets (ARID1A, FAT4, MLL, and KMT2C) revealed by large-scale cancer genomic studies. Despite extensive efforts to develop PCG-based biomarkers, only modest successes have been obtained in biomarker-assisted gastric cancer diagnosis and treatment (3,9).…”

Sustained Inhibition of HER3 and EGFR Is Necessary to Induce Regression of HER2-Amplified Gastrointestinal Carcinomas

“…Results in HER2-positive gastric cancer are less satisfactory (7)(8)(9). Although trastuzumab has been approved for gastric cancer treatment because it has been shown to provide statistically significant advantage when added to standard-of-care chemotherapy (10), the margins of benefit remain limited (9); on a worse note, the combination of lapatinib with cytotoxics failed to determine any survival improvement (11).…”

Role of Epstein Barr Virus and Gastric Carcinoma

“…La mayoría de los cánceres no cardiales son atribuibles al H. pylori 11 . Los mecanismos de carcinogénesis del H. pylori son múltiples: mediante el Cag A, la citotoxina vasculante A, genera inflamación crónica, daño oxidativo, inestabilidad genómica y cambios epigenéticos en la células epiteliales gástricas 7,12,13 .…”