Enhancing Targeted Colorectal Cancer Therapies with Natural Products: Mechanistic Pathways

Area of Science:

• Oncology
• Pharmacology
• Microbiology

Background:

• Colorectal cancer (CRC) is a major global health concern, with metastatic CRC (mCRC) posing significant treatment challenges.
• Current targeted therapies (anti-EGFR, anti-VEGF) improve outcomes but are limited by resistance, toxicity, and cost.
• There is a critical need for sustainable strategies to enhance the efficacy of mCRC treatments.

Purpose of the Study:

• To review the potential of plant-derived compounds as synergistic adjuvants in metastatic colorectal cancer therapy.
• To explore the role of phytochemicals in overcoming drug resistance and modulating the tumor microenvironment.
• To assess the impact of gut microbiota on treatment response in mCRC.

Main Methods:

• Systematic literature search of PubMed, Scopus, and Web of Science (Jan 2004 - June 2026).
• Inclusion of English-language primary studies and reviews on CRC, targeted therapy, phytochemicals, and gut microbiota.
• Analysis of preclinical and clinical data on phytochemical-targeted therapy combinations.

Main Results:

• Targeted therapies like cetuximab and bevacizumab show efficacy but face challenges with specific mutations and tumor location.
• Preclinical studies indicate potential for phytochemicals (e.g., Vitis vinifera, Dendrobium candidum, quercetin) in inhibiting angiogenesis and inducing apoptosis.
• Gut microbiome, particularly Fusobacterium nucleatum, is implicated in chemoresistance; most phytochemical combinations are supported by preclinical data.

Conclusions:

• Integrating evidence-based phytochemicals with conventional targeted therapies offers a promising, sustainable strategy for mCRC management.
• This approach may enhance efficacy, overcome resistance, and mitigate adverse effects.
• Further validation through prospective, biomarker-stratified clinical trials is essential before clinical adoption.