Abstract
Gastric cancer (GC) is one of the deadliest malignancies worldwide. Complex disease heterogeneity, late diagnosis, and suboptimal therapies result in the poor prognosis of patients. Besides genetic alterations and environmental factors, it has been demonstrated that alterations of the epigenetic machinery guide cancer onset and progression, representing a hallmark of gastric malignancies. Moreover, epigenetic mechanisms undergo an intricate crosstalk, and distinct epigenomic profiles can be shaped under different microenvironmental contexts. In this scenario, targeting epigenetic mechanisms could be an interesting therapeutic strategy to overcome gastric cancer heterogeneity, and the efforts conducted to date are delivering promising results. In this review, we summarize the key epigenetic events involved in gastric cancer development. We conclude with a discussion of new promising epigenetic strategies for gastric cancer treatment.
Highlights
Gastric cancer (GC) represents one of the most challenging issues for medical oncology, with 1 million people affected worldwide and patient 5-year survival rates ranging from 5 to 69%, depending on the stage of the disease at diagnosis [1,2]
Sci. 2020, 21, 5500 chromosomally stable tumors [18]. These subgroups showed associations with histological subtypes and tumor locations, i.e., Epstein–Barr virus (EBV) positive tumors are mostly located in the fundus or body of the stomach, with higher prevalence in men (81%); chromosomally unstable adenocarcinomas are more frequent in the gastro-esophageal junction, whereas genomically stable tumors more often present with diffuse-type histology
Phosphorylated bacterial protein CagA is able to interact with SH2-containing phosphatase (SHP-2), inducing cytoskeleton and morphological changes via inactivation of focal adhesion kinase (FAK), disturbing the tissue architecture and leading the so-called hummingbird phenotype, which is involved in gastritis patterns and cancer development [98,99]
Summary
Gastric cancer (GC) represents one of the most challenging issues for medical oncology, with 1 million people affected worldwide and patient 5-year survival rates ranging from 5 to 69%, depending on the stage of the disease at diagnosis [1,2]. The disease is characterized by a wide heterogeneity at the histopathological, onset location, and molecular levels, resulting in a complex scenario for patients’ clinical management and prognosis. Gastric cancers are defined by remarkable epigenetic alterations playing an active role both at the early stages of carcinogenesis and in the advanced disease. Several studies have highlighted the role of epigenetic dysregulation in GC onset and progression, in particular focusing on which driver epigenetic mechanisms could be targeted as a therapeutic approach for GC treatment [5,6]. To date no epigenetic therapies are available for GC clinical management, and given the importance of the gastric epigenome as a main point for molecular pathogenesis and progression, effective epigenetic treatments could open a new landscape for management of the disease
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