Induction, growth, drug resistance, and metastasis: A comprehensive summary of the relationship between STAT3 and gastric cancer

Abstract

Gastric cancer is a prevalent and highly lethal malignancy that poses substantial challenges to healthcare systems globally. Owing to its often asymptomatic nature in early stages, diagnosis frequently occurs at advanced stages when surgical intervention is no longer a viable option, forcing most patients to rely on nonsurgical treatments such as chemotherapy, targeted therapies, and emerging immunotherapies. Unfortunately, the therapeutic response rates for these treatments are suboptimal, and even among responders, the eventual development of drug resistance remains a significant clinical hurdle. Signal transducer and activator of transcription 3 (STAT3) is a widely expressed cellular protein that plays crucial roles in regulating cellular processes such as growth, metabolism, and immune function. Aberrant activation of the STAT3 pathway has been implicated in the initiation, progression, and therapeutic resistance of several cancers, with gastric cancer being particularly affected. Dysregulated STAT3 signaling not only drives tumorigenesis but also facilitates the development of resistance to chemotherapy and targeted therapies, as well as promotes metastatic dissemination. In this study, we explored the critical role of the STAT3 signaling cascade in the pathogenesis of gastric cancer, its contribution to drug resistance, and its involvement in the metastatic process. Furthermore, we assess recent advances in the development of STAT3 inhibitors and their potential application as therapeutic agents in the treatment of gastric cancer. This work provides a comprehensive overview of the current understanding of STAT3 in gastric cancer and offers a foundation for future research aimed at improving therapeutic outcomes in this challenging disease.

Keywords

• STAT3
• Gastric cancer
• MicroRNA
• Small molecule inhibitor
• Signaling pathway