Emerging Biomarkers in Genitourinary Tumors (Current Drug Metabolism)

In the last decade, the developments of drug metabolism have completely revolutionized the therapeutic scenario of Genitourinary (GU) tumors. Although the introduction of VEGF/VEGFR and mTOR inhibitors in Renal Cell Carcinoma (RCC) and of the second-generation androgen receptor inhibitors in Prostate Cancer (PCa) have led to enthusiastic results, the research of predictive and prognostic biomarkers still represents an unmet challenge with a huge medical and economic impact. Indeed, the optimization of the effectiveness of present and emerging agents, together with reducing the rate of related adverse events, will constitute a major step forward toward the personalization of cancer therapy for GU tumors. Among emerging biomarkers, Circulating Tumor Cells (CTCs), urinary biomarkers, miRNA as well as PD1/PD-L1 biomarkers seem to represent the most important candidates for such roles, as they are involved in the development, metastasization, progression and drug sensitivity of GU tumors. The authors of the four contributions, by reviewing these emerging biomarkers in GU tumors, provide insights and guidance into the future therapeutic scenario for GU tumors. PCa is a common malignancy characterized by great morphological and molecular heterogeneity that is responsible for a range of clinical behavior and response to therapies. The identification of biomarkers with a prognostic and predictive role to select the most appropriate treatment as well as to monitor its efficacy is an important issue in PCa management. CTCs can be investigated to successfully detect early tumor diagnosis, disease recurrence and to monitor metastatic spread. CTCs can also be used for biological tumor characterization, thus representing a reliable translational real-time biomarkers. The contribution by Massari et al. focuses CTCs as a potential reliable biomarker for PCa treatment assessment. In particular, the paper summarizes current data available about CTC detection, prognostic value, and potential predictive role for the management of metastatic PCa patients. Urine may represent a convenient source of biomarkers for the early detection of PCa. This is due to the fact that it contains secreted prostatic products and exfoliated tumor cells. Furthermore, urine is easy to collect with non-invasive procedures. Dr Fiorentino et al. review the current knowledge on urinary biomarkers for PCa. Several urinary biomarkers for PCa have been proposed in the past but only one (i.e., PCA3) has been approved for clinical use, even though not widely utilized in the routine. Most of the urinary biomarkers, particularly those based on proteins, have been abandoned due to the lack of confirmation trials. DNA markers have also been investigated. However, the results are not widely used in comparison with other malignancies such as bladder cancer (BC) due to the limited amount of DNA somatic alterations present in PCa. RNA biomarkers are still the most promising, particularly miRNA and AMACR mRNA. Their main weaknesses, preventing their full clinical implementation, are the lack of consistent reference standards. Recent reports have shown that miRNA has an important role in the regulation of genes by binding to complementary regions of messenger transcripts, thus repressing their translation or regulating degradation. Additionally, certain miRNAs can act as oncogenes and tumor suppressor genes. Dr Lopez-Beltran et al. review miRNA expression in BC and the potential role in clinical practice. Their comprehensive analysis of the literature has shown a differential expression between malignant and normal tissues, and that miRNAs could be the driving molecules of the BC progression. Similarly, the expression levels of miRNAs in urine and blood samples of BC patients have been demonstrated to be different from healthy people, a finding that might have diagnostic value.