Obesogens in Prostate Cancer: An Endocrine and Metabolic Threat

This review addresses the contribution of obesogenic endocrine-disrupting chemicals (EDCs) to prostate carcinogenesis. It provides an in-depth overview of obesogens, tracing their mechanisms of action and effects impacting prostate cell fate. The direct effects of obesogens in disrupting adipose tissue and metabolic homeostasis, as well as disturbing prostate cells, are discussed, along with the potential indirect effects mediated by the dysregulation of the adipose tissue. Obesogens represent a group of EDCs that interfere with endocrine and metabolic processes, underpinning the spread of obesity. Moreover, the ubiquitous presence in the environment, the ability to accumulate in adipose tissue and the broad range of effects targeting several biological pathways highlight that obesogens can be detrimental to human health beyond their action on promoting obesity. Prostate cancer (PCa) is a hormone-dependent cancer for which environmental influences and obesity are established risk factors, with emerging evidence suggesting that obesogens may affect its development and progression. The available data indicate that obesogens may contribute to the development of PCa. They can have direct actions in prostate cells modulating signalling pathways that drive tumour aggressiveness. Moreover, the adipose tissue dysregulated by obesogens can acquire an obesity-like phenotype, which may play a crucial role in facilitating tumour growth. Further research is needed to clarify the liaison between obesogen-induced dysregulation of the periprostatic adipose tissue depot and PCa aggressiveness. Unravelling this complex crosstalk will be pivotal for identifying novel therapeutic strategies and preventing aggressive PCa, especially in obese patients.