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International Journal of Molecular... Oct 2023Prostate cancer continues to pose a global health challenge as one of the most prevalent malignancies. Mutations of the Forkhead box A1 () gene have been linked to...
Prostate cancer continues to pose a global health challenge as one of the most prevalent malignancies. Mutations of the Forkhead box A1 () gene have been linked to unique oncogenic features in prostate cancer. In this study, we aimed to unravel the intricate molecular characteristics of mutant prostate cancer through comprehensive in silico analysis of transcriptomic data from The Cancer Genome Atlas (TCGA). A comparison between mutant and control groups unearthed 1525 differentially expressed genes (DEGs), which map to eight intrinsic and six extrinsic signaling pathways. Interestingly, the majority of intrinsic pathways, but not extrinsic pathways, were validated using RNA-seq data of 22Rv1 cells from the GEO123619 dataset, suggesting complex biology in the tumor microenvironment. As a result of our in silico research, we identified novel therapeutic targets and potential drug candidates for mutant prostate cancer. KDM1A, MAOA, PDGFB, and HSP90AB1 emerged as druggable candidate targets, as we found that they have approved drugs throughout the drug database CADDIE. Notably, as most of the approved drugs targeting MAOA and KDM1A were monoamine inhibitors used for mental illness or diabetes, we suggest they have a potential to cure mutant primary prostate cancer without lethal side effects.
Topics: Male; Humans; Prostatic Neoplasms; Signal Transduction; Gene Expression Regulation, Neoplastic; Tumor Microenvironment; Hepatocyte Nuclear Factor 3-alpha; Histone Demethylases
PubMed: 37958805
DOI: 10.3390/ijms242115823 -
Photodiagnosis and Photodynamic Therapy Jun 2024The global health issue of prostate cancer (PCa) requires better diagnosis and treatment. Photoacoustic imaging (PAI) may change PCa management. This review examines... (Review)
Review
The global health issue of prostate cancer (PCa) requires better diagnosis and treatment. Photoacoustic imaging (PAI) may change PCa management. This review examines PAI's principles, diagnostic role, and therapeutic guidance. PAI uses optical light excitation and ultrasonic detection for high-resolution functional and molecular imaging. PAI uses endogenous and exogenous contrast agents to distinguish cancerous and benign prostate tissues with greater sensitivity and specificity than PSA testing and TRUS-guided biopsy. In addition to diagnosing, PAI can guide and monitor PCa therapy. Its real-time imaging allows precise biopsies and brachytherapy seed placement. Photoacoustic temperature imaging allows non-invasive monitoring of thermal therapies like cryotherapy, improving treatment precision and success. Transurethral illumination probes, innovative contrast agents, integration with other imaging modalities, and machine learning analysis are being developed to overcome depth and data complexity restrictions. PAI could become an essential tool for PCa diagnosis and therapeutic guidance as the field advances.
Topics: Humans; Photoacoustic Techniques; Male; Prostatic Neoplasms
PubMed: 38821240
DOI: 10.1016/j.pdpdt.2024.104225 -
European Urology May 2024Conservative management is an option for prostate cancer (PCa) patients either with the objective of delaying or even avoiding curative therapy, or to wait until...
BACKGROUND
Conservative management is an option for prostate cancer (PCa) patients either with the objective of delaying or even avoiding curative therapy, or to wait until palliative treatment is needed. PIONEER, funded by the European Commission Innovative Medicines Initiative, aims at improving PCa care across Europe through the application of big data analytics.
OBJECTIVE
To describe the clinical characteristics and long-term outcomes of PCa patients on conservative management by using an international large network of real-world data.
DESIGN, SETTING, AND PARTICIPANTS
From an initial cohort of >100 000 000 adult individuals included in eight databases evaluated during a virtual study-a-thon hosted by PIONEER, we identified newly diagnosed PCa cases (n = 527 311). Among those, we selected patients who did not receive curative or palliative treatment within 6 mo from diagnosis (n = 123 146).
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Patient and disease characteristics were reported. The number of patients who experienced the main study outcomes was quantified for each stratum and the overall cohort. Kaplan-Meier analyses were used to estimate the distribution of time to event data.
RESULTS AND LIMITATIONS
The most common comorbidities were hypertension (35-73%), obesity (9.2-54%), and type 2 diabetes (11-28%). The rate of PCa-related symptomatic progression ranged between 2.6% and 6.2%. Hospitalization (12-25%) and emergency department visits (10-14%) were common events during the 1st year of follow-up. The probability of being free from both palliative and curative treatments decreased during follow-up. Limitations include a lack of information on patients and disease characteristics and on treatment intent.
CONCLUSIONS
Our results allow us to better understand the current landscape of patients with PCa managed with conservative treatment. PIONEER offers a unique opportunity to characterize the baseline features and outcomes of PCa patients managed conservatively using real-world data.
PATIENT SUMMARY
Up to 25% of men with prostate cancer (PCa) managed conservatively experienced hospitalization and emergency department visits within the 1st year after diagnosis; 6% experienced PCa-related symptoms. The probability of receiving therapies for PCa decreased according to time elapsed after the diagnosis.
Topics: Male; Adult; Humans; Big Data; Diabetes Mellitus, Type 2; Prostatic Neoplasms; Disease-Free Survival; Europe
PubMed: 37414703
DOI: 10.1016/j.eururo.2023.06.012 -
JAMA Network Open Oct 2023The Veterans Choice Program (VCP) was implemented in 2014 to help veterans gain broader access to specialized care outside of the Veterans Health Administration (VHA)...
IMPORTANCE
The Veterans Choice Program (VCP) was implemented in 2014 to help veterans gain broader access to specialized care outside of the Veterans Health Administration (VHA) facilities by providing them with purchased community care (CC).
OBJECTIVE
To describe the prevalence and patterns in VCP-funded purchased CC after the implementation of the VCP among veterans with prostate cancer.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used VHA administrative data on veterans with prostate cancer diagnosed between January 1, 2015, and December 31, 2018. These veterans were regular VHA primary care users. Analyses were performed from March to July 2023.
EXPOSURES
Driving distance (in miles) from residence to nearest VHA tertiary care facility. The location (VHA or purchased CC) in which treatment decisions were made was ascertained by considering 3 factors: (1) location of the diagnostic biopsy, (2) location of most of the postdiagnostic prostate-specific antigen laboratory testing, and (3) location of most of the postdiagnostic urological care encounters.
MAIN OUTCOMES AND MEASURES
The main outcome was receipt of definitive treatment and proportion of purchased CC by treatment type (radical prostatectomy [RP], radiotherapy [RT], or active surveillance) and by distance to nearest VHA tertiary care facility. Quality was evaluated based on receipt of definitive treatment for Gleason grade group 1 prostate cancer (low risk/limited treatment benefit by guidelines).
RESULTS
The cohort included 45 029 veterans (mean [SD] age, 67.1 [6.9] years) with newly diagnosed prostate cancer; of these patients, 28 866 (64.1%) underwent definitive treatment. Overall, 56.8% of patients received definitive treatment from the purchased CC setting, representing 37.5% of all RP care and 66.7% of all RT care received during the study period. Most patients who received active surveillance management (92.5%) remained within the VHA. Receipt of definitive treatment increased over the study period (from 5830 patients in 2015 to 9304 in 2018), with increased purchased CC for patients living farthest from VHA tertiary care facilities. The likelihood of receiving definitive treatment of Gleason grade group 1 prostate cancer was higher in the purchased CC setting (adjusted relative risk ratio, 1.79; 95% CI, 1.65-1.93).
CONCLUSIONS AND RELEVANCE
This cohort study found that the percentage of veterans receiving definitive treatment in VCP-funded purchased CC settings increased significantly over the study period. Increased access, however, may come at the cost of low care quality (overtreatment) for low-risk prostate cancer.
Topics: Male; United States; Humans; Aged; Veterans; United States Department of Veterans Affairs; Cohort Studies; Prostatic Neoplasms; Prostate
PubMed: 37856123
DOI: 10.1001/jamanetworkopen.2023.38326 -
Journal of Medical Internet Research Oct 2023Elicitation of patients' preferences is an integral part of shared decision-making, the recommended approach for prostate cancer decision-making. Existing decision aids... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Elicitation of patients' preferences is an integral part of shared decision-making, the recommended approach for prostate cancer decision-making. Existing decision aids for this population often do not specifically focus on patients' preferences. Healium is a brief interactive web-based decision aid that aims to elicit patients' treatment preferences and is designed for a low health literate population.
OBJECTIVE
This study used a randomized controlled trial to evaluate whether Healium, designed to target preference elicitation, is as efficacious as Healing Choices, a comprehensive education and decision tool, in improving outcomes for decision-making and emotional quality of life.
METHODS
Patients diagnosed with localized prostate cancer who had not yet made a treatment decision were randomly assigned to the brief Healium intervention or Healing Choices, a decision aid previously developed by our group that serves as a virtual information center on prostate cancer diagnosis and treatment. Assessments were completed at baseline, 6 weeks, and 3 months post baseline, and included decisional outcomes (decisional conflict, satisfaction with decision, and preparation for decision-making), and emotional quality of life (anxiety/tension and depression), along with demographics, comorbidities, and health literacy.
RESULTS
A total of 327 individuals consented to participate in the study (171 were randomized to the Healium intervention arm and 156 were randomized to Healing Choices). The majority of the sample was non-Hispanic (272/282, 96%), White (239/314, 76%), married (251/320, 78.4%), and was on average 62.4 (SD 6.9) years old. Within both arms, there was a significant decrease in decisional conflict from baseline to 6 weeks postbaseline (Healium, P≤.001; Healing Choices, P≤.001), and a significant increase in satisfaction with one's decision from 6 weeks to 3 months (Healium, P=.04; Healing Choices, P=.01). Within both arms, anxiety/tension (Healium, P=.23; Healing Choices, P=.27) and depression (Healium, P=.001; Healing Choices, P≤.001) decreased from baseline to 6 weeks, but only in the case of depression was the decrease statistically significant.
CONCLUSIONS
Healium, our brief decision aid focusing on treatment preference elicitation, is as successful in reducing decisional conflict as our previously tested comprehensive decision aid, Healing Choices, and has the added benefit of brevity, making it the ideal tool for integration into the physician consultation and electronic medical record.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05800483; https://clinicaltrials.gov/study/NCT05800483.
Topics: Male; Humans; Child; Decision Making; Decision Support Techniques; Quality of Life; Prostatic Neoplasms; Emotions
PubMed: 37862103
DOI: 10.2196/46552 -
Chemical & Pharmaceutical Bulletin 2024In the aging global population, prostate cancer is a worldwide health problem because the incidence rate of this disease increases at advanced ages. Although early-stage... (Review)
Review
In the aging global population, prostate cancer is a worldwide health problem because the incidence rate of this disease increases at advanced ages. Although early-stage prostate cancer can be treated by total prostatectomy, the surgery causes side effects, such as incontinence and dysuria, that lower QOL. Once the disease progresses to metastatic castration-resistant prostate cancer (mCRPC), there are no effective chemotherapeutic agents without systematic side effects. Therefore, targeted therapies for mCPRC are urgently needed. Traditional antibody-drug conjugate treatments for prostate cancer have been tested in clinical trials and several side effects have been observed. Meanwhile, small-molecule drug conjugates (SMDCs) have certain advantages over antibody drug conjugates in terms of non-immunogenicity, reproducibility, and permeability. In this review, prostate-specific membrane antigen-targeted SMDCs for treating prostate cancer are summarized.
Topics: Male; Humans; Prostate; Quality of Life; Reproducibility of Results; Prostatic Neoplasms; Immunoconjugates; Treatment Outcome
PubMed: 38296554
DOI: 10.1248/cpb.c23-00535 -
Journal of Controlled Release :... Jul 2024Prostate cancer (PCa) is a global health concern, ranking as the most common cancer among men in Western countries. Traditional diagnostic methods are invasive with... (Review)
Review
Prostate cancer (PCa) is a global health concern, ranking as the most common cancer among men in Western countries. Traditional diagnostic methods are invasive with adverse effects on patients. Due to the heterogeneous nature of PCa and their multifocality, tissue biopsies often yield false-negative results. To address these challenges, researchers are exploring innovative approaches, particularly in the realms of proteomics and metabolomics, to identify more reliable biomarkers and improve PCa diagnosis. Liquid biopsy (LB) has emerged as a promising non-invasive strategy for PCa early detection, biopsy selection, active surveillance for low-risk cases, and post-treatment and progression monitoring. Extracellular vesicles (EVs) are lipid-bilayer nanovesicles released by all cell types and play an important role in intercellular communication. EVs have garnered attention as a valuable biomarker resource in LB for PCa-specific biomarkers, enhancing diagnosis, prognostication, and treatment guidance. Metabolomics provides insight into the body's metabolic response to both internal and external stimuli, offering quantitative measurements of biochemical alterations. It excels at detecting non-genetic influences, aiding in the discovery of more accurate cancer biomarkers for early detection and disease progression monitoring. This review delves into the potential of EVs as a resource for LB in PCa across various clinical applications. It also explores cancer-related metabolic biomarkers, both within and outside EVs in PCa, and summarises previous metabolomic findings in PCa diagnosis and risk assessment. Finally, the article addresses the challenges and future directions in the evolving field of EV-based metabolomic analysis, offering a comprehensive overview of its potential in advancing PCa management.
Topics: Humans; Extracellular Vesicles; Prostatic Neoplasms; Biomarkers, Tumor; Male; Prognosis; Metabolomics; Animals; Liquid Biopsy
PubMed: 38768661
DOI: 10.1016/j.jconrel.2024.05.029 -
The Canadian Journal of Urology Dec 2023
Topics: Male; Humans; Prostatic Neoplasms
PubMed: 38104326
DOI: No ID Found -
Journal of Translational Medicine Jul 2023The genetic risk of aggressive prostate cancer (PCa) is hard to be assessed due to the lack of aggressiveness-related single-nucleotide polymorphisms (SNPs). Prostate...
BACKGROUND
The genetic risk of aggressive prostate cancer (PCa) is hard to be assessed due to the lack of aggressiveness-related single-nucleotide polymorphisms (SNPs). Prostate volume (PV) is a potential well-established risk factor for aggressive PCa, we hypothesize that polygenic risk score (PRS) based on benign prostate hyperplasia (BPH) or PV-related SNPs may also predict the risk of aggressive PCa or PCa death.
METHODS
We evaluated a PRS using 21 BPH/PV-associated SNPs, two established PCa risk-related PRS and 10 guideline-recommended hereditary cancer risk genes in the population-based UK Biobank cohort (N = 209,502).
RESULTS
The BPH/PV PRS was significantly inversely associated with the incidence of lethal PCa as well as the natural progress in PCa patients (hazard ratio, HR = 0.92, 95% confidence interval [CI]: 0.87-0.98, P = 0.02; HR = 0.92, 95% CI 0.86-0.98, P = 0.01). Compared with men at the top 25th PRS, PCa patients with bottom 25 PRS would have a 1.41-fold (HR, 95% CI 1.16-1.69, P = 0.001) increased PCa fatal risk and shorter survival time at 0.37 yr (95% CI 0.14-0.61, P = 0.002). In addition, patients with BRCA2 or PALB2 pathogenic mutations would also have a high risk of PCa death (HR = 3.90, 95% CI 2.34-6.51, P = 1.79 × 10; HR = 4.29, 95% CI 1.36-13.50, P = 0.01, respectively). However, no interactive but independent effects were detected between this PRS and pathogenic mutations.
CONCLUSIONS
Our findings provide a new measurement of PCa patients' natural disease outcomes via genetic risk ways.
Topics: Male; Humans; Prostatic Hyperplasia; Genetic Predisposition to Disease; Prostatic Neoplasms; Risk Factors; Risk Assessment
PubMed: 37415201
DOI: 10.1186/s12967-023-04316-y -
Current Oncology (Toronto, Ont.) Feb 2024Prostate cancer accounts for a significant proportion of cancer diagnoses in Canadian men. Over the past decade, the therapeutic landscape for the management of... (Review)
Review
Prostate cancer accounts for a significant proportion of cancer diagnoses in Canadian men. Over the past decade, the therapeutic landscape for the management of metastatic prostate cancer has undergone rapid changes. Novel strategies use hormonal agents, chemotherapy, homologous recombination repair inhibitors, and radioligand therapy or combination strategies in addition to androgen deprivation therapy. In this review, we summarize the available data addressing key therapeutic areas along the disease continuum and focus on practical aspects for general practitioners in oncology managing patients with metastatic prostate cancer.
Topics: Male; Humans; Prostatic Neoplasms; Androgen Antagonists; General Practitioners; Poly(ADP-ribose) Polymerase Inhibitors; Canada
PubMed: 38392072
DOI: 10.3390/curroncol31020078