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The reactivation of telomerase represents a key moment in the carcinogenesis process. Mutations in the central promoter region of the telomerase reverse transcriptase (TERT) gene cause telomerase reactivation in approximately 90% of solid tumors. In some of these, its prognostic and predictive role in response to treatments has already been demonstrated, in others (such as tumors of the genitourinary tract like urothelial carcinoma) data are controversial and the research is still ongoing. In the future, TERT promoter mutations and telomerase activity could have diagnostic, prognostic, and therapeutic applications in many types of cancer.We performed a review the literature with the aim of describing the current evidence on the prognostic and predictive role ofWe described the role of

The gold standard of medical therapy for advanced prostate cancer is based on the use of androgen-receptor inhibitors and taxane-based chemotherapy. Several new agents, such as enzalutamide, apalutamide, darolutamide and abiraterone, are now approved and currently used in clinical practice.We present a review of the literature on the current state of the art on the use of androgen receptors inhibitors for the treatment of castration-resistant prostate cancer. We also provide an update on recent significant progress and ongoing clinical trials, and discuss the underlying cancer biology of castration resistance.The advent of second-generation androgen receptor inhibitors has radically changed the therapeutic landscape of advanced prostate cancer. Novel strategies targeting the androgenic signaling pathway are being evaluated in order to overcome resistance mechanisms, to optimize the sequence of drugs currently available and to develop new combinational approaches to improve survival outcomes of advanced prostate cancer patients. New clinical trials, predictive biomarkers research, and real-world experience may further improve clinical outcomes and guide clinicians in the decision-making process.

Introduction: In the evolving treatment scenario of metastatic renal cell carcinoma, cabozantinib is gaining increasing attention, presenting as a cornerstone therapy, both as a monotherapy and in combination with immune-checkpoint inhibitors.Areas covered: In this review, the authors explore the role of cabozantinib in the treatment of metastatic clear cell and non-clear cell renal cell carcinoma, presenting data from the most recent clinical trials and investigating ongoing studies. They, furthermore, evaluate the pharmacokinetic, pharmacodynamic, and immunomodulatory effect of cabozantinib, as well as underlining the tolerability profile and patients' quality of life.Expert opinion: Cabozantinib's administration as a single agent is restricted to intermediate- and poor-risk patients (according to IMDC criteria). The further advent of anti-VEGF-receptor tyrosine kinase inhibitors combined with immune checkpoint inhibitor regimens (such as pembrolizumab + axitinib) has allowed to expand the use of cabozantinib, leading to its combination with nivolumab. In the next few years, more information is required to look for the application of cabozantinib-based combinations as a later-line approach in metastatic RCC patients, beside their use in the first-line setting.

Immune-based combinations, including nivolumab plus ipilimumab, pembrolizumab plus axitinib, and (at a lesser extent) avelumab plus axitinib, should be regarded among the new standards of care for first line therapy of metastatic renal cell carcinoma. Toxicity profiles are different among all these above combinations, as well as between them and targeted agents monotherapies, including sunitinib (i.e. the control arm of all the above studies). We performed a systematic review and meta-analysis with the aim to compare adverse events from immune-based combinations versus sunitinib monotherapy across four recent randomized controlled trials (CheckMate-214, Keynote-426, IMmotion-151, and JAVELIN Renal 101) of front-line treatment for metastatic renal cell carcinoma, with particular attention to those from the ipilimumab plus nivolumab combination. Beyond efficacy and activity, the ipilimumab plus nivolumab combination appears feasible, being endowed by an acceptable safety profile, in line with that of the other available options for the treatment of metastatic RCC. The different patterns of toxicities emerging from this systematic review and meta-analysis need to be kept in mind while choosing the appropriate treatment for each individual patient. Furthermore, prevention, prompt identification, and treatment of immune-related adverse events remains an area to be improved.

Introduction: Despite significant advances in the treatment of metastatic urothelial carcinoma, including the advent of immune checkpoint inhibitors, this disease is still challenging to treat and associated poor outcomes remain. Genomic characterization of advanced-stage urothelial carcinoma is widening the field of potential treatments due to the identification of novel biologic drivers. Areas covered: In this review, we explore the role of PARP, HER-2, and mTOR inhibitors in the therapeutic scenario of advanced urothelial carcinoma, as these pathways are frequently altered in urothelial carcinoma. We report ongoing clinical trials involving these agents, either in monotherapy or in combination with other compounds, highlighting the dynamic scenario of metastatic urothelial carcinoma treatment. Expert opinion: Several challenges need to be faced in the development of new potential therapeutic strategies, such as inter/intratumoral heterogeneity and the lack of validated biomarkers.