BACKGROUND/OBJECTIVES:Active surveillance (AS) has become the standard of care for many men with localised prostate cancer, aiming to avoid the overtreatment of indolent disease while maintaining oncological safety. Despite improvements in diagnostic techniques, misclassification at diagnosis and the limited ability to predict disease progression remain major challenges in AS. Novel molecular and genetic biomarkers, assessed through liquid biopsy approaches, offer the potential to refine patient selection and support risk-adapted monitoring in AS. METHODS:We conducted a narrative review of biomarkers in the context of AS for prostate cancer, framing the discussion in terms of the challenges in AS and how biomarkers may address these. PubMed and Embase were searched for English-language peer-reviewed studies published between 2000 and 2025. International guidelines (AUA, EAU, NCCN, NICE) and reference lists were reviewed manually. Priority was given to large prospective cohorts, meta-analyses, and high-impact publications. RESULTS:Blood-based assays such as PHI and the 4K score, urinary tests including ExoDx and SelectMDx, and the Prostate Urine Risk (PUR) signatures have all shown associations with disease progression or decisions to undergo earlier treatment. However, studies are often small, use surrogate endpoints, and lack validation in MRI-integrated cohorts. Biomarkers appear most informative in men with Gleason Grade 1 (GG1) disease, while evidence in GG2 cohorts is limited. Cost-effectiveness, heterogeneity of endpoints, and uncertainty in managing discordant biomarker and MRI results remain barriers to clinical adoption. CONCLUSIONS:Molecular and genetic biomarkers show promise for improving AS by reducing diagnostic misclassification and enhancing prediction of progression. Future research should define clinically relevant cut-offs, clarify integration with MRI, and evaluate longitudinal use. Demonstrating utility in contemporary cohorts could enable the development of biomarker-guided, personalised AS that maintains safety while minimising harm.

Background: Bacteria play a suspected role in the development of several cancer types, and associations between the presence of particular bacteria and prostate cancer have been reported. Objective: To provide improved characterisation of the prostate and urine microbiome and to investigate the prognostic potential of the bacteria present. Design, setting, and participants: Microbiome profiles were interrogated in sample col-lections of patient urine (sediment microscopy: n = 318, 16S ribosomal amplicon sequencing: n = 46; and extracellular vesicle RNA-seq: n = 40) and cancer tissue (n = 204). Outcome measurements and statistical analysis: Microbiomes were assessed using anaerobic culture, population-level 16S analysis, RNA-seq, and whole genome DNA sequencing. Results and limitations: We demonstrate an association between the presence of bacteria in urine sediments and higher D'Amico risk prostate cancer (discovery, n = 215 patients, p < 0.001; validation, n = 103, p < 0.001, v2 test for trend). Characterisation of the bacterial community led to the (1) identification of four novel bacteria (Porphyromonas sp. nov., Varibaculum sp. nov., Peptoniphilus sp. nov., and Fenollaria sp. nov.) that were frequently found in patient urine, and (2) definition of a patient sub-group associated with metastasis development (p = 0.015, log-rank test). The presence of five specific anaerobic genera, which includes three of the novel isolates, was associated with cancer risk group, in urine sediment (p = 0.045, log-rank test), urine extracellular vesicles (p = 0.039), and cancer tissue (p = 0.035), with a meta-analysis hazard ratio for disease progression of 2.60 (95% confidence interval: 1.39-4.85; p = 0.003; Cox regression). A limitation is that functional links to cancer development are not yet established. Conclusions: This study characterises prostate and urine microbiomes, and indicates that specific anaerobic bacteria genera have prognostic potential. Patient summary: In this study, we investigated the presence of bacteria in patient urine and the prostate. We identified four novel bacteria and suggest a potential prognostic utility for the microbiome in prostate cancer. (C) 2022 Published by Elsevier B.V. on behalf of European Association of Urology.

Aims In patients with heart failure (HF), concomitant sinus node dysfunction (SND) is an important predictor of mortality, yet its molecular underpinnings are poorly understood. Using proteomics, this study aimed to dissect the protein and phosphorylation remodelling within the sinus node in an animal model of HF with concurrent SND. Methods and results We acquired deep sinus node proteomes and phosphoproteomes in mice with heart failure and SND and report extensive remodelling. Intersecting the measured (phospho)proteome changes with human genomics pharmacovigilance data, highlighted downregulated proteins involved in electrical activity such as the pacemaker ion channel, Hcn4. We confirmed the importance of ion channel downregulation for sinus node physiology using computer modelling. Guided by the proteomics data, we hypothesized that an inflammatory response may drive the electrophysiological remodeling underlying SND in heart failure. In support of this, experimentally induced inflammation downregulated Hcn4 and slowed pacemaking in the isolated sinus node. From the proteomics data we identified proinflammatory cytokine-like protein galectin-3 as a potential target to mitigate the effect. Indeed, in vivo suppression of galectin-3 in the animal model of heart failure prevented SND. Conclusion Collectively, we outline the protein and phosphorylation remodeling of SND in heart failure, we highlight a role for inflammation in electrophysiological remodelling of the sinus node, and we present galectin-3 signalling as a target to ameliorate SND in heart failure.

Diets rich in cruciferous vegetables have been associated with a lower risk of incidence and progression of prostate cancer. Sulforaphane, an isothiocyanate derived from 4-methylsulphinylbutyl glucosinolate (glucoraphanin) that accumulates in certain of these vegetables, notably broccoli, has been implicated in their protective effects. Likewise, the consumption of garlic and its sulphur-containing compounds such as alliin have been associated with a reduction in risk of prostate cancer. In this study, we tested whether consuming glucoraphanin derived from broccoli seeds and alliin derived from garlic resulted in the occurrence of these potential bioactive compounds in the prostate, which may contribute to our understanding of the putative protective effects of these dietary components. We recruited 42 men scheduled for a trans-perineal prostate biopsy into a randomised, double-blinded, 2 × 2-factorial dietary supplement four-week intervention study, and 39 completed the study. The two active interventions were supplements providing glucoraphanin from broccoli (BroccoMax®) and alliin from garlic (Kwai Heartcare®). Following the intervention, prostate biopsy tissue was analysed for the presence of sulforaphane and its thiol conjugates and for alliin and associated metabolites. Sulforaphane occurred in significantly higher levels in the prostate tissue (both within the transition and peripheral zone) of men consuming the glucoraphanin containing supplements (p < 0.0001) compared to men not consuming these supplements. However, while alliin and alliin-derived metabolites were detected within the prostate, there was no significant difference in the concentrations of these compounds in the prostate of men consuming supplements derived from garlic compared to men not consuming these supplements.

The objective is to develop a multivariable risk model for the non-invasive detection of prostate cancer prior to biopsy by integrating information from clinically available parameters, Engrailed-2 (EN2) whole-urine protein levels and data from urinary cell-free RNA. Post-digital-rectal examination urine samples collected as part of the Movember Global Action Plan 1 study which has been analysed for both cell-free-RNA and EN2 protein levels were chosen to be integrated with clinical parameters (n = 207). A previously described robust feature selection framework incorporating bootstrap resampling and permutation was applied to the data to generate an optimal feature set for use in Random Forest models for prediction. The fully integrated model was named ExoGrail, and the out-of-bag predictions were used to evaluate the diagnostic potential of the risk model. ExoGrail risk (range 0–1) was able to determine the outcome of an initial trans-rectal ultrasound guided (TRUS) biopsy more accurately than clinical standards of care, predicting the presence of any cancer with an area under the receiver operator curve (AUC) = 0.89 (95% confidence interval(CI): 0.85–0.94), and discriminating more aggressive Gleason ≥ 3 + 4 disease returning an AUC = 0.84 (95% CI: 0.78–0.89). The likelihood of more aggressive disease being detected significantly increased as ExoGrail risk score increased (Odds Ratio (OR) = 2.21 per 0.1 ExoGrail increase, 95% CI: 1.91–2.59). Decision curve analysis of the net benefit of ExoGrail showed the potential to reduce the numbers of unnecessary biopsies by 35% when compared to current standards of care. Integration of information from multiple, non-invasive biomarker sources has the potential to greatly improve how patients with a clinical suspicion of prostate cancer are risk-assessed prior to an invasive biopsy.

Abstract Background Current diagnostic blood tests for prostate cancer (PCa) are unreliable for the early stage disease, resulting in numerous unnecessary prostate biopsies in men with benign disease and false reassurance of negative biopsies in men with PCa. Predicting the risk of PCa is pivotal for making an informed decision on treatment options as the 5-year survival rate in the low-risk group is more than 95% and most men would benefit from surveillance rather than active treatment. Three-dimensional genome architecture and chromosome structures undergo early changes during tumourigenesis both in tumour and in circulating cells and can serve as a disease biomarker. Methods In this prospective study we screened whole blood of newly diagnosed, treatment naïve PCa patients (n = 140) and cancer-free controls (n = 96) for the presence of 14,241 chromosomal loops in the loci of 425 genes. Results We have detected specific chromosome conformation changes in the loci of ETS1, MAP3K14, SLC22A3 and CASP2 genes in peripheral blood from PCa patients yielding PCa detection with 80% sensitivity and 80% specificity. Further analysis between PCa risk groups yielded prognostic validation sets consisting of HSD3B2, VEGFC, APAF1, BMP6, ERG, MSR1, MUC1, ACAT1 and DAPK1 genes that achieved 80% sensitivity and 93% specificity stratifying high-risk category 3 vs low risk category 1 and 84% sensitivity and 89% specificity stratifying high risk category 3 vs intermediate risk category 2 disease. Conclusions Our results demonstrate specific chromosome conformations in the blood of PCa patients that allow PCa diagnosis and risk stratification with high sensitivity and specificity.

Urine from patients with prostate cancer (PCa) contains gene transcripts that have been used for PCa diagnosis and prognosis. Historically, patient urine samples have been collected after a digital rectal examination of the prostate, which was thought necessary to boost the levels of prostatic secretions in the urine. We herein describe methodology that allows urine to be collected by patients at home and then posted to a laboratory for analysis. RNA yields and quality were comparable to those for post digital rectal examination urine, and there was improved sensitivity for the detection of TMPRSS2:ERG transcripts by RT-PCR. The At-Home collection protocol has opened up the potential to perform large-scale PCa studies without the inconvenience, cost, discomfort and expense of patients having to visit the clinic.

Background Prostate cancer exhibits severe clinical heterogeneity and there is a critical need for clinically implementable tools able to precisely and noninvasively identify patients that can either be safely removed from treatment pathways or those requiring further follow up. Our objectives were to develop a multivariable risk prediction model through the integration of clinical, urine-derived cell-free messenger RNA (cf-RNA) and urine cell DNA methylation data capable of noninvasively detecting significant prostate cancer in biopsy naive patients. Methods Post-digital rectal examination urine samples previously analyzed separately for both cellular methylation and cf-RNA expression within the Movember GAP1 urine biomarker cohort were selected for a fully integrated analysis (n = 207). A robust feature selection framework, based on bootstrap resampling and permutation, was utilized to find the optimal combination of clinical and urinary markers in a random forest model, deemed ExoMeth. Out-of-bag predictions from ExoMeth were used for diagnostic evaluation in men with a clinical suspicion of prostate cancer (PSA >= 4 ng/mL, adverse digital rectal examination, age, or lower urinary tract symptoms). Results As ExoMeth risk score (range, 0-1) increased, the likelihood of high-grade disease being detected on biopsy was significantly greater (odds ratio = 2.04 per 0.1 ExoMeth increase, 95% confidence interval [CI]: 1.78-2.35). On an initial TRUS biopsy, ExoMeth accurately predicted the presence of Gleason score >= 3 + 4, area under the receiver-operator characteristic curve (AUC) = 0.89 (95% CI: 0.84-0.93) and was additionally capable of detecting any cancer on biopsy, AUC = 0.91 (95% CI: 0.87-0.95). Application of ExoMeth provided a net benefit over current standards of care and has the potential to reduce unnecessary biopsies by 66% when a risk threshold of 0.25 is accepted. Conclusion Integration of urinary biomarkers across multiple assay methods has greater diagnostic ability than either method in isolation, providing superior predictive ability of biopsy outcomes. ExoMeth represents a more holistic view of urinary biomarkers and has the potential to result in substantial changes to how patients suspected of harboring prostate cancer are diagnosed.

Background Epidemiological evidence suggests that consumption of cruciferous vegetables is associated with reduced risk of prostate cancer progression, largely attributed to the biological activity of glucosinolate degradation products, such as sulforaphane derived from glucoraphanin. Because there are few therapeutic interventions for men on active surveillance for prostate cancer to reduce the risk of cancer progression, dietary approaches are an appealing option for patients. Objective We evaluated whether consumption of a glucoraphanin-rich broccoli soup for 1 y leads to changes in gene expression in prostate tissue of men with localized prostate cancer. Methods Forty-nine men on active surveillance completed a 3-arm parallel randomized double-blinded intervention study for 12 mo and underwent transperineal template biopsy procedures and …

Purpose Liquid biopsies that noninvasively detect molecular correlates of aggressive prostate cancer (PCa) could be used to triage patients, reducing the burdens of unnecessary invasive prostate biopsy and enabling early detection of high-risk disease. DNA hypermethylation is among the earliest and most frequent aberrations in PCa. We investigated the accuracy of a six-gene DNA methylation panel (Epigenetic Cancer of the Prostate Test in Urine [epiCaPture]) at detecting PCa, high-grade (Gleason score greater than or equal to 8) and high-risk (D’Amico and Cancer of the Prostate Risk Assessment] PCa from urine. Patients and Methods Prognostic utility of epiCaPture genes was first validated in two independent prostate tissue cohorts. epiCaPture was assessed in a multicenter prospective study of 463 men undergoing prostate biopsy. epiCaPture was performed by quantitative methylation-specific polymerase chain reaction in DNA isolated from prebiopsy urine sediments and evaluated by receiver operating characteristic and decision curves (clinical benefit). The epiCaPture score was developed and validated on a two thirds training set to one third test set. Results Higher methylation of epiCaPture genes was significantly associated with increasing aggressiveness in PCa tissues. In urine, area under the receiver operating characteristic curve was 0.64, 0.86, and 0.83 for detecting PCa, high-grade PCa, and high-risk PCa, respectively. Decision curves revealed a net benefit across relevant threshold probabilities. Independent analysis of two epiCaPture genes in the same clinical cohort provided analytical validation. Parallel epiCaPture analysis in urine and matched biopsy cores showed added value of a liquid biopsy. Conclusion epiCaPture is a urine DNA methylation test for high-risk PCa. Its tumor specificity out-performs that of prostate-specific antigen (greater than 3 ng/mL). Used as an adjunct to prostate-specific antigen, epiCaPture could aid patient stratification to determine need for biopsy.

Objectives(i) To assess whether exercise training attenuates the adverse effects of treatment in patients with newly diagnosed prostate cancer beginning androgen‐deprivation therapy (ADT), and (ii) to examine whether exercise‐induced improvements are sustained after the withdrawal of supervised exercise.Patients and MethodsIn all, 50 patients with prostate cancer scheduled for ADT were randomised to an exercise group (n = 24) or a control group (n = 26). The exercise group completed 3 months of supervised aerobic and resistance exercise training (twice a week for 60 min), followed by 3 months of self‐directed exercise. Outcomes were assessed at baseline, 3‐ and 6‐months. The primary outcome was difference in fat mass at 3‐months. Secondary outcomes included: fat‐free mass, cardiopulmonary exercise testing variables, QRISK®2 (ClinRisk Ltd, Leeds, UK) score, anthropometry, blood‐borne biomarkers, fatigue, and quality of life (QoL).ResultsAt 3‐months, exercise training prevented adverse changes in peak O2 uptake (1.9 mL/kg/min, P = 0.038), ventilatory threshold (1.7 mL/kg/min, P = 0.013), O2 uptake efficiency slope (0.21, P = 0.005), and fatigue (between‐group difference in Functional Assessment of Chronic Illness Therapy‐Fatigue score of 4.5 points, P = 0.024) compared with controls. After the supervised exercise was withdrawn, the differences in cardiopulmonary fitness and fatigue were not sustained, but the exercise group showed significantly better QoL (Functional Assessment of Cancer Therapy‐Prostate difference of 8.5 points, P = 0.034) and a reduced QRISK2 score (−2.9%, P = 0.041) compared to controls.ConclusionA short‐term programme of supervised exercise in patients with prostate cancer beginning ADT results in sustained improvements in QoL and cardiovascular events risk profile.

ABSTRACT Background Epidemiological evidence suggests that consumption of cruciferous vegetables is associated with reduced risk of prostate cancer progression, largely attributed to the biological activity of glucosinolate degradation products, such as sulforaphane derived from glucoraphanin. Because there are few therapeutic interventions for men on active surveillance for prostate cancer to reduce the risk of cancer progression, dietary approaches are an appealing option for patients. Objective We evaluated whether consumption of a glucoraphanin-rich broccoli soup for 1 y leads to changes in gene expression in prostate tissue of men with localized prostate cancer. Methods Forty-nine men on active surveillance completed a 3-arm parallel randomized double-blinded intervention study for 12 mo and underwent transperineal template biopsy procedures and dietary assessment at the start and end of the study. Patients received a weekly 300 mL portion of soup made from a standard broccoli (control) or from 1 of 2 experimental broccoli genotypes with enhanced concentrations of glucoraphanin, delivering 3 and 7 times that of the control, respectively. Gene expression in tissues from each patient obtained before and after the dietary intervention was quantified by RNA sequencing followed by gene set enrichment analyses. Results In the control arm, there were several hundred changes in gene expression in nonneoplastic tissue during the 12 mo. These were associated with an increase in expression of potentially oncogenic pathways including inflammation processes and epithelial–mesenchymal transition. Changes in gene expression and associated oncogenic pathways were attenuated in men on the glucoraphanin-rich broccoli soup in a dose-dependent manner. Although the study was not powered to assess clinical progression, an inverse association between consumption of cruciferous vegetables and cancer progression was observed. Conclusion Consuming glucoraphanin-rich broccoli soup affected gene expression in the prostate of men on active surveillance, consistent with a reduction in the risk of cancer progression. This trial was registered at clinicaltrials.gov as NCT01950143.

Prostate cancer has become the most common form of non-cutaneous (internal) malignancy in men, accounting for 26% of all new male visceral cancer cases in the UK. The aetiology and pathogenesis of prostate cancer are not understood, but given the age-adjusted geographical variations in prostate cancer incidence quoted in epidemiological studies, there is increasing interest in nutrition as a relevant factor. In particular, foods rich in phytochemicals have been proposed to reduce the risk of prostate cancer. Epidemiological studies have reported evidence that plant-based foods including cruciferous vegetables, garlic, tomatoes, pomegranate and green tea are associated with a significant reduction in the progression of prostate cancer. However, while there is well-documented mechanistic evidence at a cellular level of the manner by which individual dietary components may reduce the risk of prostate cancer or its progression, evidence from intervention studies is limited. Moreover, clinical trials investigating the link between the dietary bioactives found in these foods and prostate cancer have reported varied conclusions. Herein, we review the plant bioactives for which there is substantial evidence from epidemiological and human intervention studies. The aim of this review is to provide important insights into how particular plant bioactives (e.g., sulfur-containing compounds, carotenoids and polyphenols) present in commonly consumed food groups may influence the development and progression of prostate cancer.

Scope Observational studies have associated consumption of cruciferous vegetables with reduced risk of prostate cancer. This effect has been associated with the degradation products of glucosinolates—thioglycosides that accumulate within crucifers. The possible role of S‐methyl cysteine sulfoxide, a metabolite that also accumulates in cruciferous vegetables, and its derivatives, in cancer prevention is relatively unexplored compared to glucosinolate derivatives. The hypothesis that consuming a broccoli soup results in the accumulation of sulfate (a SMCSO derivative) and other broccoli‐derived metabolites in prostate tissue is tested. Methods and results Eighteen men scheduled for transperineal prostate biopsy were recruited into a 4‐week parallel single blinded diet supplementation study (NCT02821728). Nine men supplemented their diet with three 300 mL portions of a broccoli soup each week for four weeks prior to surgery. Analyses of prostate biopsy tissues reveal no detectable levels of glucosinolates and derivatives. In contrast, SMCSO is detected in prostate tissues of the participants, with significantly higher levels in tissue of men in the supplementation arm. SMCSO was also found in blood and urine samples from a previous intervention study with the identical broccoli soup. Conclusion The consequences of SMCSO accumulation in prostate tissues and its potential role in prevention of prostate cancer remains to be investigated.

Purpose: Preoperative cardiopulmonary fitness is increasingly being recognized as an important factor influencing postoperative recovery outcomes in cancer patients. The aim of this study was to explore patient perspectives of preoperative high intensity aerobic interval exercise before radical cystectomy. Materials and methods: Focus groups involving a purposive convenience sample of patients with bladder cancer (N = 14; mean age +/- SD: 72.3 +/- 6.0 years) were undertaken in a hospital education department. Data were analyzed using Framework analysis. Results: Participants identified physical (e.g., fitness) psychological (e.g., preparing for their operation) and social (e.g., peer support) benefits of the program. Key motivational factors for engaging in exercise prehabiliation were identified as social support, previous exercise experience and objective measures of progression. The need for clear information from healthcare providers to ensure that patients are adequately prepared for sessions was highlighted. Conclusions: This qualitative study provides new insights into the perspectives and experiences of patients with bladder cancer regarding participation in preoperative vigorous intensity aerobic exercise. The study yielded novel perceptions on the physical, psychological and social health benefits accruing from the exercise program and patient views on program design features, which are important for informing future interventions and implementation strategies.

Background: A critical problem in the clinical management of prostate cancer is that it is highly heterogeneous. Accurate prediction of individual cancer behaviour is therefore not achievable at the time of diagnosis leading to substantial overtreatment. It remains an enigma that, in contrast to breast cancer, unsupervised analyses of global expression profiles have not currently defined robust categories of prostate cancer with distinct clinical outcomes. Objective: To devise a novel classification framework for human prostate cancer based on unsupervised mathematical approaches. Design, setting, and participants: Our analyses are based on the hypothesis that previous attempts to classify prostate cancer have been unsuccessful because individual samples of prostate cancer frequently have heterogeneous compositions. To address this issue, we applied an unsupervised Bayesian procedure called Latent Process Decomposition to four independent prostate cancer transcriptome datasets obtained using samples from prostatectomy patients and containing between 78 and 182 participants. Outcome measurements and statistical analysis: Biochemical failure was assessed using log-rank analysis and Cox regression analysis. Result and limitations: Application of Latent Process Decomposition identified a common process in all four independent datasets examined. Cancers assigned to this process (designated DESNT cancers) are characterized by low expression of a core set of 45 genes, many encoding proteins involved in the cytoskeleton machinery, ion transport, and cell adhesion. For the three datasets with linked prostate-specific antigen failure data following prostatectomy, patients with DESNT cancer exhibited poor outcome relative to other patients (p = 2.65 x 10(-5), p = 4.28 x 10(-5), and p = 2.98 x 10(-8)). When these three datasets were combined the independent predictive value of DESNT membership was p = 1.61 x 10(-7) compared with p = 1.00 x 10(-5) for Gleason sum. A limitation of the study is that only prediction of prostate-specific antigen failure was examined. Conclusions: Our results demonstrate the existence of a novel poor prognosis category of human prostate cancer and will assist in the targeting of therapy, helping avoid treatment-associated morbidity in men with indolent disease. Patient summary: Prostate cancer, unlike breast cancer, does not have a robust classification framework. We propose that this failure has occurred because prostate cancer samples selected for analysis frequently have heterozygous compositions (individual samples are made up of many different parts that each have different characteristics). Applying a mathematical approach that can overcome this problem we identify a novel poor prognosis category of human prostate cancer called DESNT. (C) 2017 European Association of Urology. Published by Elsevier B.V.

Prevention of unnecessary biopsies and overtreatment of indolent disease remains a challenge in the management of prostate cancer. Novel non-invasive tests that can identify clinically significant (intermediate-risk and high-risk) diseases are needed to improve risk stratification and monitoring of prostate cancer patients. Here, we investigated a panel of six DNA methylation biomarkers in urine samples collected post-digital rectal exam from patients undergoing prostate biopsy, for their utility to guide decision making for diagnostic biopsy and early detection of aggressive prostate cancer.

The human prostate gland comprises three distinct anatomical glandular zones, namely the peripheral, central and transitional zones. Although prostate cancer can arise throughout the prostate, it is more frequent in the peripheral zone. In contrast, hyperplasia occurs most frequently in the transitional zone. In this paper, we test the hypothesis that peripheral and transitional zones have distinct metabolic adaptations that may underlie their different inherent predispositions to cancer and hyperplasia. In order to do this, we undertook RNA sequencing and high-throughput metabolic analyses of non-cancerous tissue from the peripheral and transitional zones of patients undergoing prostatectomy. Integrated analysis of RNAseq and metabolomic data revealed that transcription of genes involved in lipid biosynthesis is higher in the peripheral zone, which was mirrored by an increase in fatty acid metabolites, such as lysolipids. The peripheral zone also exhibited increased fatty acid catabolic activity and contained higher level of neurotransmitters. Such increased capacity for de novo lipogenesis and fatty acid oxidation, which is characteristic of prostate cancer, can potentially provide a permissive growth environment within the peripheral zone for cancer growth and also transmit a metabolic growth advantage to newly emerging clones themselves. This lipo-rich priming may explain the observed susceptibility of the peripheral zone to oncogenesis.

Strategies to improve pre-operative cardiopulmonary fitness could positively impact recovery after surgery. This study investigated the feasibility of vigorous intensity aerobic interval exercise in bladder cancer patients prior to radical cystectomy (RC).

Resistance to docetaxel is a key problem in current prostate and breast cancer management. We have recently discovered a new molecular mechanism of prostate cancer docetaxel chemoresistance mediated by the mammalian target of rapamycin (mTOR)/sphingosine-kinase-1 (SK1) pathway. Here we investigated the influence of this pathway on vascular endothelial growth factor (VEGF) production and tumour vascularisation in hormone resistant prostate and breast cancer models. Immunofluorescent staining of tumour sections from human oestrogen receptor (ER)-negative breast cancer patients showed a strong correlation between phosphorylated P70S6 kinase (mTOR downstream target), VEGF and SK1 protein expression. In hormone-insensitive prostate (PC3) and breast (MDA-MB-231 and BT-549) cancer cell lines the mTOR inhibitor RAD001 (everolimus) has significantly inhibited SK1 and VEGF expression, while low dose (5 nM) docetaxel had no significant effect. In these cell lines, SK1 overexpression slightly increased the basal levels of VEGF, but did not block the inhibitory effect of RAD001 on VEGF. In a human prostate xenograft model established in nude mice, RAD001 alone or in combination with docetaxel has suppressed tumour growth, VEGF expression and decreased tumour vasculature. Overall, our data demonstrate a new mechanism of an independent regulation of SK1 and VEGF by mTOR in hormone-insensitive prostate and breast cancers.