Abstract
Xenoestrogens and phytoestrogens are referred to as “foreign estrogens” that are produced outside of the human body and have been shown to exert estrogen-like activity. Xenoestrogens are synthetic industrial chemicals, whereas phytoestrogens are chemicals present in the plant. Considering that these environmental estrogen mimics potentially promote hormone-related cancers, an understanding of how they interact with estrogenic pathways in human cells is crucial to resolve their possible impacts in cancer. Here, we conducted an extensive literature evaluation on the origins of these chemicals, emerging research techniques, updated molecular mechanisms, and ongoing clinical studies of estrogen mimics in human cancers. In this review, we describe new applications of patient-derived xenograft (PDX) models and single-cell RNA sequencing (scRNA-seq) techniques in shaping the current knowledge. At the molecular and cellular levels, we provide comprehensive and up-to-date insights into the mechanism of xenoestrogens and phytoestrogens in modulating the hallmarks of cancer. At the systemic level, we bring the emerging concept of window of susceptibility (WOS) into focus. WOS is the critical timing during the female lifespan that includes the prenatal, pubertal, pregnancy, and menopausal transition periods, during which the mammary glands are more sensitive to environmental exposures. Lastly, we reviewed 18 clinical trials on the application of phytoestrogens in the prevention or treatment of different cancers, conducted from 2002 to the present, and provide evidence-based perspectives on the clinical applications of phytoestrogens in cancers. Further research with carefully thought-through concepts and advanced methods on environmental estrogens will help to improve understanding for the identification of environmental influences, as well as provide novel mechanisms to guide the development of prevention and therapeutic approaches for human cancers.
Highlights
Estrogens are classified as either endogenous or exogenous, according to their origins [1]
Another study investigated the potential chemo-enhancing effects and mechanisms of GEN and its analog AXP107-11, which showed an improved bioavailability of AXP107-11 for clinical use compared to GEN [129]. These findings suggest that patient-derived xenograft (PDX) models would help further the understanding of the biological effects of exogenous estrogens as relevant models of human cancers
GEN and Polychlorinated biphenyls (PCBs) can disrupt thyroid transport proteins, resulting in hormone fluctuations that have been associated with impaired neurodevelopment in offspring [224], whereas polybrominated diphenyl ethers (PBDEs) exposure has been associated with hypothyroidism [225]
Summary
Estrogens are classified as either endogenous or exogenous, according to their origins [1]. The important roles of endogenous estrogens in the etiology of breast cancer have been extensively studied, leading to the development of well-tolerated endocrine therapy for breast cancer [9] Exogenous estrogens are those which are produced outside of the human body. In addition to synthetic estrogens developed for pharmacological purposes, a group of chemicals have been found to have estrogen-like activities, such as the ability to bind to ERs and to modulate the expression of estrogen-regulated genes These exogenous and unexpected estrogen mimics include synthetic industrial compounds (xenoestrogens) and phytochemicals (phytoestrogens) [10]. They can alter the activities of ERs and send false signals, disrupting the normal estrogen response, changing physiological functions, and promoting diseases, including cancer [11]. We aim to provide thorough, updated understandings of xenoestrogens/phytoestrogens and their biological activities and mechanisms in cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
