Endocrine Abstracts

In the last years, obesity, and its associated metabolic comorbidities, have been proposed as risk factors for prostate cancer (PCa) development and linked to a more aggressive disease (e.g., PCa with poor prognosis, shorter time to develop biochemical recurrence and metastasis, and associated with increased mortality). In this sense, PCa represents the most common cancer-type in developed countries among men and it is one of the leading causes of cancer-related deaths in this collective, representing a major health problem worldwide. Unfortunately, early detection and clinical management of PCa face severe limitations. Currently, PCa initial diagnosis is mainly based on plasma prostate specific antigen (PSA) levels, a biomarker that exhibits profound drawbacks (i.e., poor specificity and predictive value). Particularly, when plasma PSA levels range between 3-10 ng/ml, also known as “grey zone”, the sensitivity, specificity, and predictive capacity of PSA is significantly worsened. Consequently, a high number of biopsies are required to detect the tumors, reducing patient quality of life. Likewise, clinical management of advanced PCa also faces major limitations, including the development of resistance to hormonal (i.e., AR pathway inhibitors) and chemical therapies (e.g., taxanes). Hence, new non-invasive and personalized diagnostic/prognostic biomarkers, as well as more effective therapeutic tools for PCa are urgently needed. In line with this idea, the endocrine/metabolic alterations that occur under an obesity state, impact normal prostate gland function; however, the precise mechanisms involved in the pathological association between obesity and cancer are still not fully elucidated. In this context, recent studies from our and other groups have demonstrated that factors belonging to different endocrine/metabolic systems (e.g., ghrelin axis, adipokines) as well as molecular components involved in the regulation of the transcriptome (e.g., miRNome, splicing machinery) are significantly altered in PCa samples, which might be useful as diagnostic/prognostic biomarkers and therapeutic targets (particularly under obesity conditions).