Abstract
Simple SummaryGastric cancer is characterized by poor survival rates despite surgery and chemotherapy. Current research focuses on biomarkers to improve diagnosis and prognosis, and to enable targeted treatment strategies. The aim of our review was to give an overview over the wide range of novel biomarkers in gastric cancer. These biomarkers are targets of a specific treatment, such as antibodies against human epidermal growth factor receptor 2. Other promising biomarkers for targeted therapies that have shown relevance in clinical trials are vascular endothelial growth factor, programmed cell death protein 1, and Claudin 18.2. There is a vast number of biomarkers based on DNA, RNA, and protein expression, as well as detection of circulating tumor cells and the immune tumor microenvironment.Overall survival of gastric cancer remains low, as patients are often diagnosed with advanced stage disease. In this review, we give an overview of current research on biomarkers in gastric cancer and their implementation in treatment strategies. The HER2-targeting trastuzumab is the first molecular targeted agent approved for gastric cancer treatment. Other promising biomarkers for targeted therapies that have shown relevance in clinical trials are VEGF and Claudin 18.2. Expression of MET has been shown to be a negative prognostic factor in gastric cancer. Targeting the PD-1/PD-L1 pathway with immune checkpoint inhibitors has proven efficacy in advanced gastric cancer. Recent technology advances allow the detection of circulating tumor cells that may be used as diagnostic and prognostic indicators and for therapy monitoring in gastric cancer patients. Prognostic molecular subtypes of gastric cancer have been identified using genomic data. In addition, transcriptome profiling has allowed a comprehensive characterization of the immune and stromal microenvironment in gastric cancer and development of novel risk scores. These prognostic and predictive markers highlight the rapidly evolving field of research in gastric cancer, promising improved treatment stratification and identification of molecular targets for individualized treatment in gastric cancer.
Highlights
Gastric cancer (GC), based on GLOBOCAN 2020 data [1], is the fifth most common cancer and the fourth most common cause of cancer-related death in the world
In the molecular evaluation of gastric adenocarcinoma as part of the The Cancer Genome Atlas (TCGA) project, PDL1/2 expression was elevated in Epstein–Barr Virus (EBV)-positive tumors, suggesting that Programmed cell death ligand 1 (PD-L1)/2 antagonists should be tested in this subgroup [7]
In conclusion and from a clinical point of view, biopsies from patients with locally advanced or metastatic GC should be tested for Human epidermal growth factor receptor 2 (HER2) overexpression, as trastuzumab is indicated in HER2-positive tumors in combination with palliative chemotherapy
Summary
Gastric cancer (GC), based on GLOBOCAN 2020 data [1], is the fifth most common cancer and the fourth most common cause of cancer-related death in the world. H. pylori infection is the strongest known risk factor for gastric cancer [2]; another pathogen associated with gastric cancer is the Epstein–Barr virus [3]. The overall survival of gastric cancer remains low, with a reported 5-year survival rate of 32% in all stages combined, and of only 6% in metastatic disease [5]. This is mostly due to the fact that gastric cancer is usually diagnosed in an advanced and unresectable stage. Most current new strategies aim to detect gastric cancer at an early stage, or to treat gastric cancer at an advanced stage. The Cancer Genome Atlas (TCGA) project has identified four major genomic subtypes of GC: Epstein–Barr Virus (EBV)-infected tumors, tumors with microsatellite instability (MSI), genomically stable tumors, and chromosomally unstable tumors, which might provide a guide to targeted agents [7]
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