NCT06982768: EMBRACE-hGC

How Epigenetic Changes in hMLH1 Connect Lab Research With Diagnosis in Gastric Cancer

Recruiting now Last updated 2 January 2026

What this trial tests

trial in Gastrectomy for Gastric Cancer in 245 participants. Currently enrolling.

Timeline

1 September 2024

Primary endpoint
31 December 2025

30 April 2026

Quick facts

Lead sponsor	Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Status	Recruiting now
Study type	OBSERVATIONAL
Enrollment	245
Start date	1 September 2024
Primary completion	31 December 2025
Estimated completion	30 April 2026
Sites	1 location across Italy

Conditions studied

• Gastrectomy for Gastric Cancer — all drugs for Gastrectomy for Gastric Cancer →
• Gastrectomy — all drugs for Gastrectomy →
• MLH1 Gene Mutation — all drugs for MLH1 Gene Mutation →
• Gastric Cancer — all drugs for Gastric Cancer →

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Who can join

18 and older, any sex, with Gastrectomy for Gastric Cancer or Gastrectomy. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

DNA methylation is one of the key mechanisms that are thought to underlie the association between aging and cancer. Several methylation-based measures of biological aging have been developed and have demonstrated an association with mortality and, in some cases, with cancer incidence. Accordingly, CpG promoter hypermethylation is a well-known mechanism of gene inactivation in carcinogenesis.

Gastric cancer has been classified in different molecular phenotypes based on genetic and epigenetic characteristics. One of these subtypes is characterized by a high grade of microsatellite instability (MSI-H). In gastric cancer, the MSI-H status is mostly caused by methylation of the hMLH1 gene promoter (between 71% and 78%), that is also considered the representative of a gastric-specific CpG island methylation pattern (CIMP). Gastric cancer with hMLH1 hypermethylation is frequently expressed in the MSI-H phenotype but also reported in the MSI-L type. Hypermethylation has been associated with advanced age, dietary habits, smoking and alcohol consumption. Moreover, other studies on GI cancer (colorectal, rectal and gastric) have associated hMLH1 hypermethylation with decreased levels of folate, vitamin C and niacin. Last, increased oxidative stress has been proposed as one of the possible initiators of cancer development and progression through epigenetic mechanism as hypermethylation. From a clinical standpoint, MSI-H gastric cancers have been associated with increased resistance to standard chemotherapy and increased immunogenicity, representing a hypothetic ideal target to immunotherapy, that has documented clinical efficacy for this subtype. However, some authors have suggested that MSI-H GCs without hMLH1 hypermethylation and GCs with hMLH1 hypermethylation could be different in terms of clinicopathologic characteristics and biological behavior. In addition, the specific role of hMLH1 hypermethylation in resistance to standard chemotherapy is unknown, as well as its potential adjunctive role in the chemoresistance of hypermethylated - but MSI-L - tumors.

Identifying risk factors for hMLH1 hypermethylated GC could have relevant implications in terms of disease prevention and even reversal of the hypermethylation mechanisms through natural as well as synthetic compounds. It could also identify a predictive tool to better stratify patients for expected sensitivity to specific chemotherapy (or biological therapy) regimens. Therefore, this preliminary study aims to determine if the development of hMLH1-methylated GC is associated with specific clinicopathologic characteristics and environmental habits. It also aims to report on the biological behavior of these tumors, as well as on their chemosensitivity to platin-based chemotherapy regimens.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.