Multifunctional Natural and Synthetic Compounds Targeting Oxidative Stress, Inflammation, and Microbial Dysbiosis in Gastrointestinal Cancers

Gastrointestinal (GI) cancers, including stomach, colorectal, pancreatic, liver, and esophageal, account for about 25% of global cancer cases and 35% of all cancer-related deaths. They are shaped by a complex interplay between chronic inflammation, microbial dysbiosis, and oxidative stress, which are processes contributing to tumor initiation, progression, and resistance to therapy. Conventional therapies with well-known cytostatics can cause severe toxicity and resistance, prompting a shift toward therapies that restore biological homeostasis and target multiple molecular pathways simultaneously. Thus, both natural and synthetic compounds are currently widely sought as agents that can act in a multi-directional manner in gastrointestinal cancers. Bioactive phytochemicals including phenolic acids, flavonoids, alkaloids, saponins, terpenoids and others, frequently exhibiting pleiotropic biological activities, as well as chemically modified derivatives or targeted nanomedicines designed to improve oral bioavailability, may be covered by this scope. Notably, plant-derived compounds obtained using advanced plant biotechnology approaches, including plant in vitro cultures, represent a promising and sustainable source of highly active secondary metabolites with potential anticancer properties. At the same time, selected microbial metabolites, including short-chain fatty acids and polyphenol-derived metabolites, may contribute to the maintenance of intestinal homeostasis and modulation of antitumor immune responses.

The purpose of this Research Topic is to present studies focusing on natural and synthetic compounds capable of modulating key biological mechanisms involved in cancer development, targeting oxidative stress, inflammation and related signaling pathways, as well as the gut microbiota. Particular attention is given to compounds that support beneficial gut bacteria or inhibit the growth of pathogenic microorganisms associated with gastrointestinal cancer development and progression. The Research Topic places special emphasis on tumor initiation, progression, and therapeutic resistance.

• Plant extracts, secondary metabolites and synthetic compounds as anticancer agents, especially against human gastric, colon and pancreatic cancers
• Antioxidant and anti-inflammatory activity of natural and synthetic compounds in the prevention of gastrointestinal cancers
• Natural and synthetic compounds targeting bacterial strains and fungal species of the digestive tract involved in gastrointestinal cancer development and progression
• Effects of natural and synthetic compounds on tumor microenvironment in gastrointestinal cancers
• Plant in vitro cultures as a sustainable source of bioactive compounds with anticancer potential
• Phytochemical profiling and metabolomic approaches in the identification of anticancer compounds
• Mechanisms of action of natural and synthetic compounds targeting oxidative stress, inflammation, and tumor progression
• Mechanisms of action of natural and synthetic compounds in gastrointestinal cancer prevention and therapy
• Interactions between gut microbiota and gastrointestinal cancer development
• Biotechnological strategies for enhanced production of secondary metabolites (e.g., elicitation, bioreactors)
• In vitro and in vivo evaluation of biological activity, including anticancer, antioxidant, anti-inflammatory, and antimicrobial effects
• Strategies to improve bioavailability and efficacy of bioactive compounds (e.g., nanoformulations)
• Translational and preclinical studies on bioactive compounds in gastrointestinal oncology
• Microbiota-mediated biotransformation of bioactive compounds and the biological activity of microbiota-derived metabolites in gastrointestinal cancer-related processes

Please note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal.

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• Case Report
• Clinical Trial
• Editorial
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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Case Report
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: in vitro and in vivo studies, plant in vitro cultures, phytochemistry, chemoprevention, microbiota-derived metabolites

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.