Multifaceted mechanisms by which environmental endocrine-disrupting chemicals promote cancer progression: crosstalk among carcinogenesis, immunity, and metabolic reprogramming: narrative mini-review

Endocrine-disrupting chemicals (EDCs) are ubiquitous and highly persistent environmental contaminants. Human exposure occurs through multiple routes, including dietary ingestion, water consumption, inhalation, and dermal contact, posing sustained health risks characterized by chronic, low-dose, and cumulative mixture exposure. Through interference with endocrine signaling and related biological pathways, EDCs have been implicated in the development and progression of several health outcomes, particularly reproductive, metabolic, neurodevelopmental, and hormone-related disorders. Of particular concern is their involvement in oncogenesis; throughout tumor progression, EDCs facilitate immune dysregulation and metabolic reprogramming via complex interactions across multiple targets and signaling pathways. Elucidating these underlying regulatory mechanisms is imperative for developing robust preventive strategies. This review synthesizes evidence regarding bisphenols, per- and polyfluoroalkyl substances (PFAS), heavy metals, pesticides, phthalates, polychlorinated biphenyls (PCBs), and other emerging pollutants. We specifically highlight their mechanistic roles across three critical domains: carcinogenesis, immune modulation, and metabolic reprogramming. Given the long latency periods, significant inter-individual variability, and synergistic mixture effects associated with EDC exposure, current risk assessments and causal inferences remain constrained. Future research must integrate high-precision exposure science, prospective longitudinal cohorts, and multi-omic mechanistic validation, while incorporating critical developmental windows and mixture-exposure frameworks. Ultimately, such advancements will provide a more reliable evidence base for exposure prevention, regulatory decision-making, and risk stratification and intervention strategies for exposure-related malignancies.