Microplastics as emerging carcinogens: from environmental pollutants to oncogenic drivers

The widespread environmental pollution of microplastics (MPs) and nanoplastics (NPs) has become a major public health issue, with increasing evidence associating their bioaccumulation with cancer onset. This review offers a thorough examination of the etiological contributions of MPs/NPs in carcinogenesis, clarifying their mechanistic roles in in vitro, in vivo, and patient-derived evidences. Relevant studies were systematically identified and screened following the PRISMA 2020 guidelines to ensure methodological transparency and quality. We highlighted recent discoveries that emphasize the varied accumulation of MPs in several human cancer tissues, including lung, colorectal, gastric, cervical, breast, pancreatic, prostate and penile malignancies. These particles induce harmful biological effects by chronic inflammation, oxidative stress, genotoxicity, disturbance of lipid metabolism, and alteration of the tumor immunological microenvironment. Significantly, MPs/NPs disrupt various oncogenic signaling pathways, particularly NF-κB, PI3K/Akt/mTOR, Wnt/β-catenin, and p53, therefore facilitating tumor initiation, development, and metastasis. In vitro and in vivo studies have corroborated the carcinogenic potential of MPs/NPs, illustrating their capacity to cause cellular transformation, augment metastatic characteristics, and modify drug resistance pathways in cancer cells. Furthermore, the detection of MPs in human biological matrices, including blood, placenta, and tumor tissues, highlights direct human exposure and potential systemic effects. This review emphasizes the mechanistic insights with therapeutic significance, addressing current knowledge gaps in the field. Future research must prioritize biomarker identification, patient-centered investigations, therapeutic targeting, and the formulation of regulatory policies to alleviate the health hazards linked to microplastic exposure. Understanding the intricate relationship between MPs/NPs and cancer biology could facilitate the development of novel cancer prevention and management strategies related to environmental contamination.