Molecular Characterization of Gastric Carcinoma: Therapeutic Implications for Biomarkers and Targets

Abstract

Palliative chemotherapy is the mainstay of treatment of advanced gastric carcinoma (GC). Monoclonal antibodies including trastuzumab, ramucirumab, and pembrolizumab have been shown to provide additional benefits. However, the clinical outcomes are often unpredictable and they can vary widely among patients. Currently, no biomarker is available for predicting treatment response in the individual patient except human epidermal growth factor receptor 2 (HER2) amplification and programmed death-ligand 1 (PD-L1) expression for effectiveness of trastuzumab and pembrolizumab, respectively. Multi-platform molecular analysis of cancer, including GC, may help identify predictive biomarkers to guide selection of therapeutic agents. Molecular classification of GC by The Cancer Genome Atlas Research Network and the Asian Cancer Research Group is expected to identify therapeutic targets and predictive biomarkers. Complementary to molecular characterization of GC is molecular profiling by expression analysis and genomic sequencing of tumor DNA. Initial analysis of patients with gastroesophageal carcinoma demonstrates that the ratio of progression-free survival (PFS) on molecular profile (MP)-based treatment to PFS on treatment prior to molecular profiling exceeds 1.3, suggesting the potential value of MP in guiding selection of individualized therapy. Future strategies aiming to integrate molecular classification and profiling of tumors with therapeutic agents for achieving the goal of personalized treatment of GC are indicated.

WITHDRAWN: Evaluation of PAX8 Expression Promotes the Proliferation of Stomach Cancer cells

“…At presentRecently, patients with stomach cancer patients treated with treated by surgery, chemotherapy and other measurestreatment generally showed poor prognosis and high recurrencetumor recurrence rate- [3][4][5]. As malignant proliferation is one of the characteristics distinguishing tumor cells from normal somatic cells, in recent years, the development and application of molecular drugs targeting cell proliferation have greatly improved the therapeutic effect of stomach cancer and the survival prognosis of patients [6,7]. Therefore, in-depth exploration of the molecular mechanism of stomach cancer cell proliferation may potentially open up give new possibilities for developing new stomach cancer treatment and improving patient survival [8].…”

HER2 Heterogeneity in Personalized Therapy of Gastro-Oesophageal Malignancies: An Overview by Different Methodologies

“…In EA some mutated genes, such as TP53 (72%), ELMO1 (25%), DOCK2 (12%), CDKN2A (12%), ARID1A (9%), SMAD4 (8%) and PIK3CA (6%), have been identified [102], although no molecular biomarker has been supported in oncological trials. Furthermore, the amplification of KRAS (21%), HER2 (19%), EGFR (16%), CND1 (10%) and MET (6%) as well as the loss of SMAD4 (34%), CDKN2A (32%) and ARID1A (10%) have been recorded [118,119].…”

SOX13 dependent PAX8 expression promotes the proliferation of gastric carcinoma cells

“…At present, patients with gastric cancer treated by surgery, chemotherapy and other measures generally show poor prognosis and high tumour recurrence rate [3][4][5]. As malignant proliferation is one of the characteristics distinguishing tumour cells from normal somatic cells, in recent years, the development and application of molecular drugs targeting cell proliferation have greatly improved the therapeutic effect of gastric cancer and the survival prognosis of patients [6,7]. Therefore, in-depth exploration of the molecular mechanism of gastric cancer cell proliferation may potentially open up new possibilities for developing new gastric cancer treatment and improving patient survival [8].…”