The role of di-(2-ethylhexyl) phthalate in cancer initiation and progression: Mechanisms and health implications

The increasing prevalence of cancer has been linked to various environmental factors associated with modern industrial and societal advancements. Di-(2-ethylhexyl) phthalate (DEHP), a commonly used plasticizer, is one such environmental contaminant with potential carcinogenic effects. While epidemiological studies have suggested a positive association between DEHP exposure and cancer risk, the specific role of DEHP in cancer initiation and progression requires further clarification. This review systematically examines the relationship between DEHP exposure and cancer, highlighting key mechanisms involved in tumorigenesis. DEHP has been found to influence several critical aspects of cancer biology, including cell proliferation, apoptosis, metastasis, invasion, epithelial-mesenchymal transition, angiogenesis, drug resistance, immune regulation, and cancer stem cell maintenance. These carcinogenic effects are mediated through multiple pathways, such as the PI3K/AKT signaling pathway, estrogen receptor activation, epigenetic modifications, oxidative stress, and inflammation. By elucidating the molecular mechanisms underlying DEHP's role in cancer, this review aims to contribute to the development of targeted prevention and intervention strategies to mitigate the cancer risks associated with DEHP exposure.