Gastrointestinal Cancers: From Pathogenesis to Treatment

Dear Colleagues,

Gastric cancer remains one of the most lethal malignancies worldwide, continuing to pose a major challenge in clinical oncology. Despite advances in diagnosis and therapy, the prognosis for patients with advanced or recurrent gastric cancer remains poor. Systemic multidrug chemotherapy is widely applied as a standard treatment; however, its efficacy is often hampered by tumor heterogeneity and the frequent emergence of chemoresistance.

Accumulating evidence highlights the pivotal role of gastric cancer stem cells (CSCs) in mediating chemoresistance, tumor relapse, and metastasis. CSCs possess unique capabilities for self-renewal, differentiation, and tumor initiation, enabling them to survive conventional treatments and repopulate tumors. Among the key regulatory pathways, nuclear factor erythroid 2-related factor 2 (Nrf2) has emerged as a crucial transcription factor maintaining cellular redox balance by regulating antioxidant enzyme expression. Enhanced Nrf2 activity within CSCs contributes to their resistance to oxidative stress and therapy-induced cytotoxicity. Nrf2-mediated extracellular vesicles (EVs) also play a pivotal role in facilitating communication between CSCs and tumor microenvironment cells.

The interplay between CSCs and antioxidant transcriptional networks, such as Nrf2 signaling, represents a novel conceptual framework for understanding gastric cancer progression and therapeutic resistance. Exploring this crosstalk could unveil innovative strategies for targeting redox homeostasis and stemness in gastric tumors. Furthermore, increasing evidence suggests that nutritional or natural compounds capable of modulating antioxidant pathways and CSC activity may offer promising preventive or therapeutic benefits in gastrointestinal cancers.

In line with these emerging insights, this Special Issue welcomes original research articles, reviews, and communications focusing on novel treatment strategies, molecular mechanisms of chemoresistance, and the pathogenesis of gastrointestinal cancers. Studies exploring the biological regulation of CSCs, redox signaling, EVs-gastric cancer cell communication and the therapeutic potential of natural compounds are particularly encouraged.

Dr. Mingwei Lin
Dr. Cheng-Che Lee
Guest Editors

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