Cancer and Environmental Xenobiotics: Mechanisms, Controversies, and Innovations

Although cancer biology has advanced considerably, the impact of environmental toxins on carcinogenesis remains underrecognized and scattered across disciplines. Evidence increasingly shows that chronic exposure to a broad range of toxins-including persistent organic pollutants, heavy metals, pesticides, phthalates, microplastics, and fine particulate matter (PM2.5), which significantly contributes to cancer initiation, progression, and treatment resistance. This review synthesizes mechanistic, molecular, and epidemiological findings from 2015 to 2025, identified through systematic searches of PubMed, Scopus, Web of Science, and MeSH. Key pathways include oxidative stress-mediated DNA damage, epigenetic reprogramming (DNA methylation, histone modifications, miRNA dysregulation), hormone receptor modulation, chronic inflammation, immune evasion, and tumor microenvironment remodeling. Case studies of benzene, arsenic, aflatoxins, pesticides, and microplastics detail exposure routes, molecular targets, and associated cancers, highlighting significant public health risks. Ongoing debates persist regarding safe exposure thresholds, latency periods, and the effects of mixed toxin exposures. The review also highlights recent innovations in environmental oncology, including AI-based predictive models, CRISPR screens for susceptibility genes, organoid/3D models, green chemistry interventions, and real-time exposure monitoring, which provide mechanistic insight and inform early detection and personalized prevention strategies. Additionally, regional data gaps, particularly in low- and middle-income countries, indicate the need for stronger interdisciplinary collaboration. By integrating molecular mechanisms, epidemiology, and technological advances, this review offers a comprehensive framework for understanding toxin-induced carcinogenesis and guiding future research, public health policy, and preventive strategies.