Early Stage Gastric Adenocarcinoma: Clinical and Molecular Landscapes

Authors

Yuki Hirata
Ayesha Noorani
Shumei Song
Linghua Wang
Jaffer A Ajani

Publication Date

7-1-2023

Journal

Nature Reviews Clinical Oncology

DOI

10.1038/s41571-023-00767-w

PMID

37264184

PMCID

PMC11869628

PubMedCentral® Posted Date

2-28-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Gastric adenocarcinoma, even when diagnosed at an early (localized) disease stage, poses a major health-care burden with cure rates that remain unsatisfactorily low, particularly in Western countries. This lack of progress reflects, among other aspects, the impracticality of early diagnosis, considerable variations in therapeutic approaches that is partly based on regional preferences, and the ingrained heterogeneity of gastric adenocarcinoma cells and their associated tumour microenvironment (TME). Clinical trials have long applied empirical interventions with the assumption that all early stage gastric adenocarcinomas are alike. Despite certain successes, the shortcomings of these approaches can potentially be overcome by targeting the specific molecular subsets of gastric adenocarcinomas identified by genomic and/or multi-omics analyses, including microsatellite instability-high, Epstein-Barr virus-induced, DNA damage repair-deficient, HER2-positive and PD-L1-high subtypes. Future approaches, including the availability of sophisticated vaccines, novel antibody technologies, agents targeting TME components (including fibroblasts, macrophages, cytokines or chemokines, and T cells) and novel immune checkpoint inhibitors, supported by improved tissue-based and blood-based diagnostic assays, seem promising. In this Review, we highlight current knowledge of the molecular and cellular biology of gastric adenocarcinomas, summarize the current approaches to clinical management of the disease, and consider the role of novel management and/or treatment strategies.

Keywords

Humans, Epstein-Barr Virus Infections, Herpesvirus 4, Human, Stomach Neoplasms, Adenocarcinoma, Genomics, Tumor Microenvironment

Published Open-Access

yes

Recommended Citation

Hirata, Yuki; Noorani, Ayesha; Song, Shumei; et al., "Early Stage Gastric Adenocarcinoma: Clinical and Molecular Landscapes" (2023). Faculty, Staff and Student Publications. 5128.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5128