Title:Outlook on Epigenetic Therapeutic Approaches for Treatment of Gastric Cancer
Volume: 18
Issue: 1
Author(s): Petra Hudler*
Affiliation:
- Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana,Slovenia
Keywords:
Gastric cancer, DNA methylation, miRNA, CpG island, epigenetic modification, Helicobacter pylori, therapeutics.
Abstract: The incidence of gastric cancer has been declining globally in the last decades. Despite
the improvements in the diagnostic procedures, most cases are still detected at advanced stages due
to lack of specific symptoms associated with early phases of tumour development. Consequently,
gastric cancer poses a major health burden worldwide due to high mortality rates. Continuing advances
in high-throughput technologies are revealing an intricate network of genetic and epigenetic
changes associated with carcinogenesis. In addition, several risk factors, both environmental and genetic,
have been recognized, which promote accumulation of diverse alterations affecting the expression
of oncogenes, tumour suppressor genes, DNA repair genes, and other genes, implicated in
normal gastric cell functions. A plethora of aberrant molecular events found in patients with this disease
and intragenic heterogeneity of tumours from individuals are delaying the development of targeted
biological therapies. Frequent occurrence of characteristic CpG island methylator phenotypes
(CIMP phenotypes) in gastric cancers, particularly in association with Helicobacter pylori or EBV
infection, could lead to introduction of epigenetic modulators into standard treatment regimens used
against early and advanced forms of adenocarcinomas. This review highlights aberrant DNA methylation
events in the development of gastric tumours and addresses the different aspects associated
with the application of therapeutic epigenetic modulation in the management of the disease.
