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Metabolic requirements for prostate cancer cell fitness

Final Report Summary - CANCERMETAB (Metabolic requirements for prostate cancer cell fitness)

Metabolism is an emerging hallmark of cancer. This compilation of biological processes generates products that can be measured and monitored with various techniques. Importantly, enzymatic reactions constitute an important subject for pharmacological manipulation, and have inspired the design of hundreds of drugs that are currently used in the clinic. With this premise, understanding the metabolic changes underlying the pathogenesis and progression of cancer can provide us with novel approaches to diagnose, monitor and treat this deadly disease. In the course of the ERC Starting grant Cancermetab, we have developed scientific strategies, methodologies and resources to deconstruct the molecular basis of prostate cancer metabolism.

Our research has shed light on:
i) the relationship between oncogenic signalling and metabolic reprogramming that sustains prostate cancer initiation and progression,
ii) the association of chronic treatments frequently employed in prostate cancer patients and the progression of the disease,
iii) the relationship between nutritional alterations leading to obesity and the progression of prostate cancer, and
iv) the existence of molecular biomarkers in urine that can inform about aspects of this disease.

Overall, our studies to date have contributed to elucidate molecular determinants of prostate cancer progression and are the basis for our future research. We envision metabolism as a tool and a target to fight prostate cancer, and our research in metastatic prostate cancer suggests that tumors develop vulnerabilities as they progress that are pharmacological amenable. It is worth noting that a clinical prospective study spear-headed in collaboration with Basurto University Hospital (Spain) has provided us with access to liquid biopsy from prostate cancer, which has served to identify secreted molecules in urine that inform about the molecular properties of an individual prostate cancer. Our data strongly suggests that we can monitor and manipulate cancer cell nutrition and nutrients utilization as a mean to detect and treat this deadly disease.