The Chemopreventive and Antitumor Potential of Cranberry ( Vaccinium Macrocarpon Aiton) in Gastrointestinal Cancers: A Review of Molecular Mechanisms, Preclinical Evidence, and Commercial Perspectives

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Gastrointestinal cancers constitute a significant global health challenge, with 4.8 million new cases and 3.4 million deaths reported in 2018. Despite therapeutic advances, survival rates remain poor due to late-stage diagnosis and inadequate prevention strategies. The economic burden is substantial, with cancer-related macroeconomic costs projected at $25.2 trillion globally between 2020–2050, including 10.9% attributed to colorectal cancer alone. This comprehensive review evaluates the chemopreventive and therapeutic potential of cranberry (Vaccinium macrocarpon Aiton) against gastrointestinal malignancies. Cranberries contain bioactive compounds including A-type proanthocyanidins, flavonols (quercetin, myricetin), anthocyanins, and triterpenoids that exhibit multifaceted anticancer properties. These phytochemicals modulate key oncogenic pathways (PI3K/Akt/mTOR, NF-κB/COX-2, MAPK), induce cell cycle arrest, and promote apoptosis. In preclinical colorectal cancer models, cranberry interventions significantly reduced tumor incidence through anti-inflammatory and pro-apoptotic mechanisms. Cranberry proanthocyanidins demonstrated context-dependent effects in esophageal adenocarcinoma, with gut microbiota serving as critical mediators of polyphenol metabolism. The established functional food market ($280.7 billion, 2021) provides viable commercial pathways for cranberry-based interventions, offering cost-effective alternatives to conventional treatments. This review synthesizes current evidence and identifies opportunities for developing economically viable chemopreventive strategies against gastrointestinal cancers.