Emerging Hallmarks of Metabolic Reprogramming in Prostate Cancer.

Prostate cancer (PCa) is the most common male malignancy and the fifth leading cause of cancer death in men worldwide. Prostate cancer cells are characterized by a hybrid glycolytic/oxidative phosphorylation phenotype determined by androgen receptor signaling. An increased lipogenesis and cholesterogenesis have been described in PCa cells. Many studies have shown that enzymes involved in these pathways are overexpressed in PCa. Glutamine becomes an essential amino acid for PCa cells, and its metabolism is thought to become an attractive therapeutic target. A crosstalk between cancer and stromal cells occurs in the tumor microenvironment because of the release of different cytokines and growth factors and due to changes in the extracellular matrix. A deeper insight into the metabolic changes may be obtained by a multi-omic approach integrating genomics, transcriptomics, metabolomics, lipidomics, and radiomics data.

MUC1 Tissue Expression and Its Soluble Form CA15-3 Identify a Clear Cell Renal Cell Carcinoma with Distinct Metabolic Profile and Poor Clinical Outcome.

An altered metabolism is involved in the development of clear cell renal carcinoma (ccRCC). MUC1 overexpression has been found to be associated with advanced disease and poor prognosis. In this study, we evaluated the metabolomic profile of human ccRCC, according to MUC1 expression, and integrated it with transcriptomic data. Moreover, we analyzed the role of MUC1 in sustaining ccRCC aggressiveness and the prognostic value of its soluble form CA15-3. Integrated metabolomic and transcriptomic analysis showed that MUC1-expressing ccRCC was characterized by metabolic reprogramming involving the glucose and lipid metabolism pathway. In addition, primary renal cancer cells treated with a small interfering RNA targeting MUC1 (siMUC1) migrated and proliferated at a slower rate than untreated cancer cells. After cisplatin treatment, the death rate of cancer cells treated with siMUC1 was significantly greater than that of untreated cells. Kaplan-Meier curves showed significant differences in CSS and PFS among groups of patients with high versus low levels of CA15-3. In a multivariate analysis, CA15-3 was an independent adverse prognostic factor for cancer-specific and progression-free survival. In conclusion, MUC1 expressing ccRCC is characterized by a particular metabolic reprogramming. The inhibition of MUC1 expression decreases cell motility and viability and improves cisplatin susceptibility, suggesting that this pathway can regulate de novo chemotherapy resistance in ccRCC.

Metabolomic Approaches for Detection and Identification of Biomarkers and Altered Pathways in Bladder Cancer.

Metabolomic analysis has proven to be a useful tool in biomarker discovery and the molecular classification of cancers. In order to find new biomarkers, and to better understand its pathological behavior, bladder cancer also has been studied using a metabolomics approach. In this article, we review the literature on metabolomic studies of bladder cancer, focusing on the different available samples (urine, blood, tissue samples) used to perform the studies and their relative findings. Moreover, the multi-omic approach in bladder cancer research has found novel insights into its metabolic behavior, providing excellent start-points for new diagnostic and therapeutic strategies. Metabolomics data analysis can lead to the discovery of a "signature pathway" associated with the progression of bladder cancer; this aspect could be potentially valuable in predictions of clinical outcomes and the introduction of new treatments. However, further studies are needed to give stronger evidence and to make these tools feasible for use in clinical practice.

Novel Insights into Autophagy and Prostate Cancer: A Comprehensive Review.

Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible.

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

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.

The dark side of lipid metabolism in prostate and renal carcinoma: novel insights into molecular diagnostic and biomarker discovery.

INTRODUCTION: Lipidomics focuses on the in-depth analysis of lipids, which are crucial macromolecules involved in a wide range of metabolic pathways. The increased intracellular accumulation of different classes of lipids in renal cell carcinoma (RCC) and prostate cancer (PCa) cells may be caused by elevated absorption or by increased de novo lipogenesis as a consequence of lipid metabolism reprogramming. The involvement of cholesterol metabolism in cancer's aberrant pathways has also been demonstrated. AREAS COVERED: This review provides an update on the most important lipidomics studies and applications in RCC and PCa, with a particular focus on how knowledge of aberrant lipid pathways may be used to identify biomarkers and novel therapeutic targets. In addition, the application of this methodologies have led to novel cancer subtypes identification and patient's risk stratification. Tracking tumor progression using specific biofluid metabolite profiles offers a huge translational opportunity for urological malignancies. EXPERT OPINION: Lipidomics is a promising branch of 'omics' approach and should include in next decade new standardized analysis methods and randomized clinical trials in order to reach the aim to use this high-throughput technique in patient-tailored therapy perspective.

Immune Checkpoint Inhibitors in Renal Cell Carcinoma: Molecular Basis and Rationale for Their Use in Clinical Practice.

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.

Single-Port Robotic Surgery: General Principles and Troubleshooting.

The da Vinci single-port (SP) system (Intuitive Surgical, Sunnyvale, CA) is the newest robotic platform released and approved for use in the urologist's armimentarium. This article (and complementary video) aims to summarize the most common problems that have been encountered at the University of Illinois at Chicago when using the SP system. Moreover, solutions to these issues will be presented.

Corrigendum: A Narrative Approach to Describe QoL in Children With Chronic ITP.

[This corrects the article DOI: 10.3389/fped.2019.00163.].

A Narrative Approach to Describe QoL in Children With Chronic ITP.

Objective: Primary immune thrombocytopenia (ITP) is a hemorrhagic disorder. Spontaneous recovery within 12 months occurs in the majority of pediatric patients. Nevertheless, in 20-30% of children the disease is chronic. The impact extends to the patients' families, whose everyday life, in terms of interpersonal relationships and financial status, is adversely affected. This study investigated the ability of a narrative instrument to improve the quality of life of pediatric chronic ITP patients and their families and quantified the familial burden imposed by the illness. Method: A quantitative survey and a narrative plot delivered through an online platform were adopted for the analysis. Results: Pediatricians of ten Italian Hematologic Centers explained the projects to patients and their family in the outpatient clinic. 70 caregivers of children with ITP filled the ad-hoc questionnaire. Data from 53 caregivers revealed the emotional impact of pediatric chronic ITP. The narrative approach highlighted the specific resources used by patients and their families to cope with the disease and its chronicity. Discussion: Caregivers underlined the need for "humaneness" in their interactions with clinical personnel. The majority of respondents provided positive feedback regarding the narrative project, defining the experience as "liberating" and improving their quality of life.