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DOI: 10.1055/s-0044-1790566
Gastric Cancer: Molecular Characterization, Therapeutic Innovations, and Perspectives
Authors
Funding The authors declare that they did not receive funding from agencies in the public, private or non-profit sectors to conduct the present study. Clinical Trials None.

Abstract
Introduction Gastric cancer is the fifth most common neoplasm and the fourth leading cause of cancer-related death in the world. The present review aims to offer to the oncologic community the molecular characterization of gastric cancer, the therapeutic innovations and the perspectives for the systemic therapy for gastric cancer.
Materials and Methods We searched for articles in the PubMed database using Medical Subject Headings (MeSH). The latest publications and proceedings of meetings were also reviewed.
Results The cornerstone of the systemic therapy for gastric cancer is the dual combination of fluoropyrimidines and platin-based chemotherapy. Nevertheless, it is recommended that gastric cancer patients are tested for human epidermal growth factor receptor 2 (HER2), high-frequency microsatellite instability (MSI-H), programmed cell death-ligand 1(PD-L1), and claudin 18.2 expression. If HER2-positive, trastuzumab plus pembrolizumab should be added to the doublet chemotherapy. Anti-programmed cell death-1 (anti-PD-1) therapy, such as nivolumab or pembrolizumab, should also be added to chemotherapy in MSI-H and in the PD-L1-positive patients. Patients who present overexpression of claudin 18.2 should be treated with the combination of zolbetuximab and oxaliplatin-based chemotherapy. Immunotherapy may also be considered in patients with high tumor mutational burden. Clinical trials evaluating fibroblast growth factor receptor 2 (FGFR2) inhibitors and the dual inhibition anti-PD-1 and anti-T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (anti-TIGIT) are promising.
Conclusions The clinical applicability of precision medicine in gastric cancer has risen in the past few decades, leading to substantial improvements in the efficacy of the systemic therapy. Testing patients for biomarkers is paramount for the appropriate management of advanced disease. Ongoing clinical trials evaluating new therapeutic strategies are promising and offer optimism for the patients affected by this challenging disease.
Author's Contributions
ETC, SJA, and AAJ: collection and assembly of data, conception and design, data analysis and interpretation, final approval of the manuscript, manuscript writing, and provision of study materials or patient.
Publication History
Received: 08 March 2024
Accepted: 27 June 2024
Article published online:
16 December 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)
Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil
Emily Tonin da Costa, Sergio Jobim de Azevedo, Alexandre A. Jácome. Gastric Cancer: Molecular Characterization, Therapeutic Innovations, and Perspectives. Brazilian Journal of Oncology 2024; 20: s00441790566.
DOI: 10.1055/s-0044-1790566
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