Pharmacometabolomics Applied to Personalized Medicine in Urological Cancers

Abstract

Prostate cancer (PCa), bladder cancer (BCa), and renal cell carcinoma (RCC) are the most common urological cancers, and their incidence has been rising over time. Surgery is the standard treatment for these cancers, but this procedure is only effective when the disease is localized. For metastatic disease, PCa is typically treated with androgen deprivation therapy, while BCa is treated with chemotherapy, and RCC is managed primarily with targeted therapies. However, response rates to these therapeutic options remain unsatisfactory due to the development of resistance and treatment-related toxicity. Thus, the discovery of biomarkers with prognostic and predictive value is needed to stratify patients into different risk groups, minimizing overtreatment and the risk of drug resistance development. Pharmacometabolomics, a branch of metabolomics, is an attractive tool to predict drug response in an individual based on its own metabolic signature, which can be collected before, during, and after drug exposure. Hence, this review focuses on the application of pharmacometabolomic approaches to identify the metabolic responses to hormone therapy, targeted therapy, immunotherapy, and chemotherapy for the most prevalent urological cancers.

Revolutionizing Blood Collection: Innovations, Applications, and the Potential of Microsampling Technologies for Monitoring Metabolites and Lipids

“…Most of the studies are focused on the quantification of the drugs in blood or serum using DBS [ 92 ], but in recent years, pharmacometabolomics has emerged, aiming at the evaluation of the metabolic fingerprints following drug administration [ 93 ]. Even with some limitations, i.e., the standard protocol for sample preparation and storage, environment influence, and ethnicity, this type of study could be useful to evaluate drug toxicity and pharmacokinetics, but also predict the pharmaceutical answer and its pharmacodynamics [ 94 ].…”

Metabolomics and Proteomics in Prostate Cancer Research: Overview, Analytical Techniques, Data Analysis, and Recent Clinical Applications

“…In precision medicine, analyzing the perturbations in low-molecular-weight endogenous and exogenous metabolite levels is crucial for selecting biomarkers to predict responses and monitor a patient's health status during treatment [93]. Prostate cancer has been extensively studied using pharmacometabolomic approaches, focusing on understanding the metabolic changes associated with therapeutic response and castration resistance [94]. In vitro studies using PCa cell lines have examined the effects of inhibitors on metabolomic profiles, revealing alterations in amino acids, fatty acids, and other metabolites.…”

“…Human studies, mainly in serum, plasma, and tissue, have analyzed the metabolic changes occurring under hormone therapy and chemotherapy regimens, identifying potential biomarkers for therapeutic responses and revealing the metabolic alterations associated with treatment outcomes, such as changes in bile acid metabolism, steroid synthesis, and ketogenesis. Understanding these metabolic differences can inform the development of personalized treatment strategies for PCa [94]. On the other hand, Pharmacoproteomics is a field that explores the interactions between drugs and the proteome; it involves studying how drugs influence protein expression, post-translational modifications, and interactions within a biological system, aiming to understand the molecular mechanisms of drug action, identify potential drug targets, and optimize therapeutic strategies by analyzing the proteomic changes induced by drugs.…”

Renal Cell Carcinoma as a Metabolic Disease: An Update on Main Pathways, Potential Biomarkers, and Therapeutic Targets

“…The acquisition of drug resistance is a crucial factor in RCC pharmacologic management and is responsible for the disease's poor prognosis and limited long-term responses [198,199]. As a result, the first-line therapy for RCC includes tyrosine kinase inhibitors such as sunitinib, pazopanib, tivozanib, and cabozantinib, as well as mTOR inhibitors such as temsirolimus and everolimus [200,201].…”