Clear cell renal cell carcinoma (ccRCC) is the most frequent histological kidney cancer subtype. Over the last decade, significant progress has been made in identifying the genetic and metabolic alterations driving ccRCC development. In particular, an integrated approach using transcriptomics, metabolomics, and lipidomics has led to a better understanding of ccRCC as a metabolic disease. The metabolic profiling of this cancer could help define and predict its behavior in terms of aggressiveness, prognosis, and therapeutic responsiveness, and would be an innovative strategy for choosing the optimal therapy for a specific patient. This review article describes the current state-of-the-art in research on ccRCC metabolic pathways and potential therapeutic applications. In addition, the clinical implication of pharmacometabolomic intervention is analyzed, which represents a new field for novel stage-related and patient-tailored strategies according to the specific susceptibility to new classes of drugs.

Renal cell carcinoma (RCC) is the seventh most common cancer in men and the ninth most common cancer in women worldwide. There is plenty of evidence about the role of the immune system in surveillance against tumors. Thanks to a better understanding of immunosurveillance mechanisms, immunotherapy has been introduced as a promising cancer treatment in recent years. Renal cell carcinoma (RCC) has long been thought chemoresistant but highly immunogenic. Considering that up to 30% of the patients present metastatic disease at diagnosis, and around 20–30% of patients undergoing surgery will suffer recurrence, we need to identify novel therapeutic targets. The introduction of immune checkpoint inhibitors (ICIs) in the clinical management of RCC has revolutionized the therapeutic approach against this tumor. Several clinical trials have shown that therapy with ICIs in combination or ICIs and the tyrosine kinase inhibitor has a very good response rate. In this review article we summarize the mechanisms of immunity modulation and immune checkpoints in RCC and discuss the potential therapeutic strategies in renal cancer treatment.

Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains.

Among risk factors (apart from smoking) likely involved in bladder cancer (BCa), metabolic syndrome (MS), obesity and type 2 diabetes mellitus (T2DM) have been explored with contrasting results. In spite of these studies, there is little data on the association between nonalcoholic fatty liver disease (NAFLD), its main driver, i.e., insulin resistance (IR), and BCa. Implanting a cross-sectional retrospective study we tried to investigate both NAFLD and IR prevalence in a hospital based population of BCa patients. We studied laboratory data from 204 patients with histologically confirmed non metastatic BCa and 50 subjects with no BCa, but with bladder diseases (no Ca BD). We evaluated the presence of NAFLD by the triglycerides/glucose Index (TyG Index), using a cut-off of 0.59 and by the Aspartate Aminotransferase/Alanine Aminotransferase AST/ALT ratio. IR was assessed by the same TyG Index (cut-off 4.68) and the triglycerides/High-Density Lipoprotein HDL ratio (cut-off 2.197). The diagnosis of impaired fasting glucose (IFG), condition of prediabetes, as well as that of T2DM was assessed according to canonical guidelines. The TyG Index predicted NAFLD presence in both groups (p = 0.000), but the BCa group showed a major percentage of NAFLD cases with respect to no Ca BD group (59% versus 40%). A greater proportion of IR (47%) in BCa group than in no Ca BD one (37%) was evidenced by the TyG Index with its median value significantly different (p = 0.0092). This high rate of IR in the BCa group was confirmed by the triglycerides/HDL ratio (p = 0.02). Prediabetes and T2DM were more prevalent in the BCa group than no Ca BD group (p = 0.024). In this study a consistent NAFLD presence was found in BCa patients. This is an important comorbidity factor that deserves further consideration in prospective studies. The higher prevalence of NAFLD, IR, prediabetes and T2DM in the BCa group evidences the need that these disorders should be reckoned as adjunct factors that could impact on this cancerous disease.

Although appreciable attempts in screening and diagnostic approaches have been achieved, prostate cancer (PCa) remains a widespread malignancy, representing the second leading cause of cancer-related death in men. Drugs currently used in PCa therapy initially show a potent anti-tumor effect, but frequently induce resistance and PCa progresses toward metastatic castration-resistant forms (mCRPC), virtually incurable. Liquid biopsy has emerged as an attractive and promising strategy complementary to invasive tissue biopsy to guide PCa diagnosis and treatment. Liquid biopsy shows the ability to represent the tumor microenvironment, allow comprehensive information and follow-up the progression of the tumor, enabling the development of different treatment strategies as well as permitting the monitoring of therapy response. Liquid biopsy, indeed, is endowed with a significant potential to modify PCa management. Several blood biomarkers could be analyzed for diagnostic, prognostic and predictive purposes, including circulating tumor cells (CTCs), extracellular vesicles (EVs), circulating tumor DNA (ctDNA) and RNA (ctRNA). In addition, several other body fluids may be adopted (i.e., urine, sperm, etc.) beyond blood. This review dissects recent advancements and future perspectives of liquid biopsies, highlighting their strength and weaknesses in PCa management.

Globally, clear-cell renal cell carcinoma (ccRCC) represents the most prevalent type of kidney cancer. Surgery plays a key role in the treatment of this cancer, although one third of patients are diagnosed with metastatic ccRCC and about 25% of patients will develop a recurrence after nephrectomy with curative intent. Molecular-target-based agents, such as tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), are recommended for advanced cancers. In addition to cancer cells, the tumor microenvironment (TME) includes non-malignant cell types embedded in an altered extracellular matrix (ECM). The evidence confirms that interactions among cancer cells and TME elements exist and are thought to play crucial roles in the development of cancer, making them promising therapeutic targets. In the TME, an unfavorable pH, waste product accumulation, and competition for nutrients between cancer and immune cells may be regarded as further possible mechanisms of immune escape. To enhance immunotherapies and reduce resistance, it is crucial first to understand how the immune cells work and interact with cancer and other cancer-associated cells in such a complex tumor microenvironment.