Targeting cancer pathways with phytochemicals: Molecular mechanisms and clinical potential

Objectives Cancer progression is driven by dysregulated signaling networks that control proliferation, apoptosis, inflammation, angiogenesis, invasion, oxidative stress adaptation, and epigenetic remodeling. Phytochemicals have attracted increasing attention as anticancer candidates because they can modulate multiple molecular pathways, although their clinical translation remains limited by bioavailability, formulation, and validation challenges. This review summarizes the molecular mechanisms and clinical potential of major anticancer phytochemicals in relation to cancer-associated signaling pathways. Methods A structured narrative review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar for literature published from 1 January 2000 through 16 July 2025. After deduplication and title/abstract and full-text screening against prespecified eligibility criteria, 36 publications were included. Evidence was synthesized by phytochemical class, molecular target, exposure-defined mechanism, formulation strategy, and translational relevance. Results Preclinical evidence indicates that phytochemicals can regulate PI3K/Akt/mTOR, NF-κB, MAPK/ERK, STAT3, Nrf2–Keap1, Wnt/β-catenin, apoptotic, angiogenic, metastatic, inflammatory, and epigenetic pathways. These compounds may induce mitochondrial and death-receptor apoptosis, inhibit cell-cycle progression, suppress VEGF-mediated angiogenesis, modulate epithelial–mesenchymal transition, regulate oxidative stress, and influence DNMT/HDAC activity and non-coding RNA networks. Early clinical studies suggest biological activity in selected contexts, mainly through biomarker modulation and pharmacodynamic endpoints, but definitive clinical efficacy remains insufficiently established. Conclusion Phytochemicals show promise as mechanism-defined investigational adjuncts in cancer therapy. Future translation requires standardized formulations, exposure-matched mechanistic validation, biomarker-guided trials, ClinicalTrials.gov-linked reporting, and integration of proteomics, pharmacogenomics, and multi-omics approaches.