Search Results (1,153)

Background: Lower urinary tract symptoms (LUTSs) are among the most common urological complaints in older men, frequently arising from benign prostatic hyperplasia (BPH) or prostate cancer (PCa). While both conditions share overlapping symptomatology, the way each condition progresses and is managed differs considerably. In sub-Saharan Africa, data on the relative burden of BPH and PCa among men presenting with LUTSs are scarce. This study aimed to determine the prevalence of histologically confirmed BPH and PCa among men presenting with LUTSs at a major tertiary referral center in Tanzania and to explore the association between specific urinary symptoms and histopathological diagnoses. Methods: A retrospective cross-sectional study was conducted at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania, reviewing medical records of adult male patients aged ≥50 years who presented with LUTSs and underwent prostatic biopsy between January and December 2023. A total of 133 patients were included through simple random sampling from an eligible population of 260. Data on demographics, comorbidities, International Prostate Symptom Score (IPSS), serum prostate-specific antigen (PSA), prostate volume, and histopathological biopsy outcomes were extracted using a purpose-built digital form. This study was conducted in compliance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Results: Most patients (39.8%) were aged 70 to 79 years. Hypertension was the most frequent comorbidity among those with chronic disease (31.65%), followed by diabetes mellitus (12.03%). The mean serum PSA was 465.1 ng/mL (SD = 1610.1), and the mean prostate volume was 80.6 cm³ (SD = 75.6). Histopathologically, 57.9% of biopsies were benign and 40.6% were malignant. The most commonly reported IPSS symptoms were urinary frequency (78.2%), weak stream (78.2%), and incomplete emptying (64.7%). Most patients (59.4%) had severe IPSSs. Statistically significant associations were observed between biopsy outcomes and incomplete emptying (p = 0.011), frequency (p = 0.014), weak stream (p = 0.022), nocturia (p = 0.001), urge incontinence (p = 0.004), and post-void dribbling (p < 0.001). IPSS severity was significantly associated with biopsy diagnosis (p < 0.001), with 63% of malignant cases presenting with moderate symptom scores. Conclusions: BPH was the predominant histopathological diagnosis among men presenting with LUTSs at this tertiary center, while prostate cancer accounted for a substantial minority of cases. Certain individual LUTSs, particularly nocturia, urge incontinence, and post-void dribbling, demonstrated significant associations with malignant histopathology. These findings underscore the necessity for systematic histopathological evaluation in all men presenting with LUTSs in resource-limited settings, irrespective of symptom severity. Full article

Castrate-resistant prostate cancer (PCa) is a critical situation in which many patients will relapse. Hormonal androgen deprivation therapy (HADT) is the gold standard of care when a patient relapses, following primary surgical or radiation therapy. Usually, the benefits from HADT are poor and recurrent disease after HADT treatment is termed castrate-resistant prostate cancer (CRPC), which is in most cases fatal. The therapeutic regimens for CRPC include chemotherapy with docetaxel, immunotherapy agent sipuleucel-T, the taxane cabazitaxel, the CYP17 inhibitor abiraterone acetate and the androgen receptor (AR) antagonist enzalutamide. Thus, it is imperative to study the inherent property of prostate cancer cells, to resist therapy and reconsider the therapeutic protocols (continuous v’s intermittent). We make use of a hybrid mathematical model which consists of an extension of a very potent ordinary differential equation (ODE) Baez–Kuang model, combined with two Game Theory components: the Minority Game for adaptive behavior and the Axelrod model for heterogeneity behavior. Our study suggests that increasing tumor adaptability, through Minority Game dynamics, improves short-term prostatic-specific antigen (PSA) control and stabilizes therapy cycles. However, this comes at the cost of driving the tumor to a homogeneous, androgen-independent (AI) state, which is therapy-resistant. Conversely, maintaining heterogeneity, via Axelrod dynamics, sustains a mixed population, with androgen-dependent (AD) cells persisting longer and potentially delaying resistance emergence. Full article

Background/Objectives: An accurate preoperative assessment of prostate cancer malignancy is crucial for risk stratification and selection of the optimal treatment strategy. This study assessed the concordance of Gleason scores between MRI–TRUS fusion biopsy and radical prostatectomy specimens, and identified clinical and histopathological factors associated with post-procedural Gleason score upgrading. Methods: This retrospective analysis involved patients who underwent transperineal MRI–TRUS fusion biopsy followed by radical prostatectomy from 2020 to 2025. Concordance, upgrading, and downgrading of the Gleason score were assessed by comparing biopsy results with the final histopathological examination. Clinical parameters (age, PSA level, prostate volume, and PSA density) and histopathological features of biopsies (Gleason score and percentage of prostate lobes affected by cancer) were analyzed. Multivariate logistic regression models were stratified by PSA level (<10 ng/mL and >10 ng/mL). Results: Gleason score concordance was found in 53.1% of the 603 patients analyzed, upgrading in 29.9%, and downgrading in 17.1%. Higher Gleason scores on biopsy were independently associated with a lower risk of upgrading in the entire cohort and in both PSA subgroups. Larger tumor extent on biopsy was associated with a lower risk of upgrading, with heterogeneous dependencies between prostate lobes. The other clinical parameters showed no independent association with upgrading. Conclusions: Gleason score upgrading remains common after radical prostatectomy. The risk of this progression is primarily related to the histopathological features of the biopsy rather than to baseline clinical parameters, reflecting the limitations of biopsy as a sampling method and the biological heterogeneity of prostate cancer. Full article

Background/Objectives: Prostate cancer is one of the most common malignancies diagnosed in men worldwide. Brachytherapy (BT), particularly low-dose rate (LDR)-BT, has been shown to be a successful treatment. The aim of this study was to evaluate the effectiveness of BT treatment in localized prostate cancer patients from a single-center Portuguese cohort. Methods: This was a retrospective study that evaluated prostate cancer patients followed up at the Center for the Treatment of Urological Diseases, Coimbra, Portugal, who underwent LDR-BT between November 2007 and March 2024. Overall survival (OS), biochemical recurrence-free survival (BRFS) and complications post-LDR BT treatment were evaluated during patients’ follow-up time. Results: A total of 1343 patients treated with LDR-BT were recruited. Global OS and BRFS rates were 98.4% and 87.7%, respectively. A reduced frequency of complications such as lower urinary tract symptoms, erectile dysfunction, acute urinary retention, radiation proctitis and stress urinary incontinence were described. High OS (>98%) and BRFS rates were observed particularly in low and intermediate disease risk. Prostate-specific antigen (PSA) serum levels > 20 ng/mL, Gleason score (GS) ≥ 8 and clinical tumor stage (cT) ≥ T2c were identified as the strongest predictors of death and/or biochemical recurrence. Conclusions: BT is an effective treatment in localized prostate cancer patients, with comparable outcomes and consistent with the OS and BRFS rates reported in the current literature for radical prostatectomy and external beam radiotherapy approaches, and with a reduced frequency of complications. PSA serum levels > 20 ng/mL, GS ≥ 8 and cT stage ≥ T2c can be used as strong predictors of death and/or biochemical recurrence during patients’ follow-up. Full article

Gold nanoparticles (AuNPs) have been extensively studied in cancer treatment research since they have special physicochemical characteristics such as facile surface functionalization with various chemical groups, low toxicity, favorable biocompatibility, and the ability to passively accumulate in tumors through the enhanced permeability and retention (EPR) effect. Prostate cancer cells exhibit an overexpression of the Prostate-Specific Membrane Antigen (PSMA), which therefore represents an ideal candidate for the development of nanoplatforms targeting PSMA overexpressed on these cells. Lutetium-177 (¹⁷⁷Lu) is a β-particle emitter with a half-life of 6.7 days. This radionuclide is very promising for the development of theranostic platforms as it emits β⁻ particles, which are suitable for therapy, and γ-photons, capable of SPECT imaging. The combination of ¹⁷⁷Lu with AuNPs functionalized with PSMA for targeted delivery offers a promising tool for both diagnosis and therapy of prostate cancer. In this study, we focused on the synthesis and in vitro evaluation of PSMA-targeted AuNPs radiolabeled with ¹⁷⁷Lu. The AuNPs were functionalized with the TADOTAGA chelator, which enables effective radiolabeling with the radiometal, as well as with a PSMA molecule, which comprises the PSMA targeting moiety (vehicle) of the nanoconstruct. Radiolabeling of the functionalized AuNPs with ¹⁷⁷Lu was fast and robust. Subsequent studies focused on the in vitro stability and cellular interaction with two prostate cancer cell lines with different PSMA expression levels, in both 2D and 3D cell cultures, to assess effective targeting. Results indicate that radiolabeled AuNPs exhibit selective interaction with PSMA-expressing cells and present a stronger in vitro cytotoxic effect when functionalized with the PSMA molecule, confirming their potential as theranostic agents and warranting further investigation in LNCaP tumor-bearing mice. Full article

Purpose: Prostate-specific membrane antigen (PSMA) is a well-established molecular target in prostate cancer (PCa). Both radionuclide imaging and near-infrared fluorescence (NIRF) imaging offer high sensitivity for in vivo tumor detection. PSMA-targeted dual-modality probes integrating these two imaging techniques provide complementary preoperative and intraoperative tumor visualization, thereby improving surgical guidance in PCa. In this study, we aimed to develop a novel dual-labeled PSMA probe combining radioactive and fluorescent properties to achieve precise tumor delineation during radical prostatectomy (RP). Methods: A high-affinity PSMA-targeted fluorescent probe (PSMA-DF) was synthesized using solid-phase synthesis. Subsequent radiolabeling with the radionuclide [⁶⁸Ga]Ga yielded the successful generation of a dual-modal PSMA-targeted molecular probe, namely [⁶⁸Ga]Ga-PSMA-DF. The probe was systematically evaluated both in vitro and in vivo, and its safety profile was assessed through acute toxicity testing. Tumor-bearing nude mouse models were established using PSMA-positive 22Rv1 and PSMA-negative PC-3 PCa cell lines. Imaging performance, tumor-targeting specificity, and biodistribution of the probe were comprehensively evaluated using micro-PET imaging, in vivo fluorescence imaging, and biodistribution studies. Results: High-quality and high-purity PSMA-DF was successfully prepared, which exhibited excellent optical properties. Following radiolabeling with [⁶⁸Ga]Ga, a dual-modality radionuclide-fluorescence probe ([⁶⁸Ga]Ga-PSMA-DF) was successfully constructed. In vitro cellular uptake studies demonstrated that 22Rv1 cells had relatively high uptake of the probe, reaching 7.34 ± 0.55 IA%/10⁶ cells at 120 min. In contrast, PC-3 cells and blocked 22Rv1 cells displayed minimal uptake, confirming the specific targeting ability of the probe. In vivo evaluations were conducted on tumor-bearing mice using micro-PET/CT and NIRF imaging. The results revealed that [⁶⁸Ga]Ga-PSMA-DF achieved high specific tumor accumulation in 22Rv1 xenografts, with the peak tumor uptake (SUVmax = 1.748 ± 0.132) and tumor-to-muscle ratio (11.542 ± 1.511) observed at 120 min. Notably, high-contrast fluorescence imaging was also achieved at later time points, yielding a tumor-to-background ratio (TBR) of 6.559 ± 1.415 at 48 h. Notably, ex vivo biodistribution data were consistent with in vivo imaging findings. Conclusions: This preclinical study demonstrates that [⁶⁸Ga]Ga-PSMA-DF exhibits high and specific uptake in PCa models, supporting its potential as a dual-modality tracer for both PET/CT imaging and real-time intraoperative fluorescence guidance during PCa surgery. Full article

Background: Transperineal magnetic resonance (MRI)/ultrasound (US) fusion-guided prostate biopsy has emerged as a promising alternative to the transrectal approach by improving lesion targeting and reducing infectious complications. However, real-world data addressing factors that influence the detection of clinically significant prostate cancer (csPCa), including imaging characteristics and procedural experience, remain limited. Objective: To evaluate the diagnostic performance, safety profile, and independent predictors of csPCa detection in patients who underwent transperineal MR/US fusion-guided prostate biopsy, with particular emphasis on PIRADS category, prostate-specific antigen (PSA) level, and procedural learning curve. Methods: In this study, patient data were prospectively recorded in a routinely maintained institutional database, while the present analysis was conducted retrospectively. A total of 136 patients with clinical suspicion of prostate cancer—defined as elevated prostate-specific antigen (PSA), abnormal digital rectal examination, or PIRADS ≥3 on multiparametric MRI—underwent transperineal MR/US fusion-guided biopsy between January 2023 and October 2024. Results: Prostate cancer was detected in 45.5% of patients, whereas csPCa was identified in 32.3%. The PIRADS category emerged as the strongest independent predictor of csPCa detection, with PIRADS-5 lesions showing a significantly greater likelihood of csPCa than PIRADS-3 lesions (OR 6.70, p = 0.006). The PSA level was also independently associated with csPCa detection (OR 1.06 per ng/mL increase, p = 0.033). Although csPCa detection rates increased across learning curve groups, procedural experience was not an independent predictor after adjustment. The procedure demonstrated a favorable safety profile, with a low rate of infectious and noninfectious complications despite minimal use of antibiotic prophylaxis. The multivariable model showed moderate explanatory power and acceptable overall classification accuracy. Conclusions: Transperineal MR/US fusion-guided prostate biopsy provides reliable detection of clinically significant prostate cancer with a low complication rate and consistent performance across different stages of institutional experience. The PIRADS category and PSA level remain key determinants of csPCa detection, supporting the integration of MRI-based risk stratification into contemporary prostate cancer diagnostic methods. Full article

Given ongoing uncertainty about the benefits and harms of prostate-specific antigen (PSA) screening, this systematic review updates the evidence to inform guideline recommendations for adults aged ≥ 18 years in primary care. We searched multiple bibliographic databases from inception to 30 May 2022, with an update on 24 July 2024, for randomized controlled trials (RCTs) and comparative observational studies evaluating PSA-based screening with or without adjunctive technologies such as magnetic resonance imaging (MRI). Studies were selected in duplicate, with data extraction and quality assessment verified by a second reviewer; risk of bias and evidence certainty were assessed using study design-specific tools and GRADE. Four RCTs and one cohort study (17 articles) were included: ERSPC, PLCO and CAP compared PSA screening with no screening, while STHLM3-MRI evaluated a risk-based test combined with MRI targeted biopsy. Meta-analysis showed 0.96 fewer prostate cancer deaths per 1000 individuals invited to screen, corresponding to a 12% relative reduction over 9.5–22 years (RR 0.88, 95% CI 0.81–0.95). One trial estimated 2.3% to 10.3% overdiagnosis over 10–14 years. Overall certainty of evidence was low or very low. PSA screening may offer a small mortality benefit, but uncertainty and variable harms limit confidence, underscoring the need for high-quality evidence, particularly for MRI and risk-based screening strategies. Full article

Background/Objectives: Urinary continence recovery after robot-assisted radical prostatectomy (RARP) follows a progressive trajectory that is often simplified into binary outcomes. Modeling continence recovery as an ordered process may better reflect post-operative functional patterns and identify clinically relevant predictors. Methods: We retrospectively analyzed 180 patients undergoing extraperitoneal single-port RARP. At 6 months, continence recovery was classified into three ordered categories: early continence, late continence, and persistent incontinence. Multivariable ordinal logistic regression was used to identify independent predictors of continence recovery. The primary model included nerve-sparing (NS) status, postoperative complications, age, and prostate volume. Sensitivity analyses were performed by sequentially replacing prostate volume with body mass index, surgical case number, or preoperative prostate-specific antigen (PSA). An interaction between NS and age group was also tested. Results: NS surgery was the factor most strongly associated with favorable continence recovery (p < 0.001), followed by absence of post-operative complications (p = 0.003). Younger age and larger prostate volume were also independently associated with improved continence recovery. Sensitivity analyses confirmed the robustness of the primary model, as replacement of prostate volume with body mass index, surgical case number, or PSA did not improve model performance and did not alter the effect of NS surgery. No significant interaction between NS and age group was observed. Conclusions: Continence recovery after extraperitoneal RARP is primarily associated with NS surgery and an uncomplicated post-operative course, with age and prostate volume providing additional refinement. Modeling continence as an ordinal outcome offers a clinically meaningful framework for evaluating functional recovery after prostatectomy. Full article

Background/Objectives: Prostate cancer testing relies on prostate-specific antigen testing and digital rectal examination, which have limited specificity and face cultural or geographic barriers to access. We developed a non-invasive urine-based liquid biopsy assay using engineered hydrogel arrays and machine learning to detect disease-specific biochemical profiles. Methods: We collected voided urine samples from 283 participants at 26 U.S. urology practices prior to prostate biopsy. Random forest classifiers trained on 184 biopsy-confirmed cancer cases and 75 controls analyzed colorimetric signatures. Results: Across all Gleason grades (6–10), the assay achieved 97.8% sensitivity and 53.3% specificity. Performance varied by grade: high-grade cancers showed 97.3% specificity, while low-to-intermediate grades demonstrated 94.0% sensitivity. Conclusions: This accessible, culturally-appropriate platform could expand prostate cancer detection in diverse populations while reducing unnecessary invasive biopsies. Full article

Field-effect transistor (FET) biosensors using graphene have become one of the most promising biosensing platforms for the early diagnosis of diseases with features such as high sensitivity, label-free detection and application compatibility with point-of-care systems. Herein, we critically discuss recent advances in graphene FET (GFET) biosensor development toward clinically relevant biomarkers associated with representative diseases including cancer, neurodegenerative disease, infectious disease, and inflammatory conditions. Recent progress was reviewed to evaluate GFET architectures, surface functionalization methods, and detection quality. The biomarkers explored were clusterin in Alzheimer’s disease, thrombin in coagulopathy, estrogen receptor α (ER-α) in breast cancer, Carcinoembryonic antigen in lung cancer, microRNAs for malignant tumors, exosomes derived from HepG2 for the hepatocellular carcinoma (HCC) cell line, interleukin-6 (IL-6) for chronic obstructive pulmonary disease (COPD), Polyclonal antibodies and antigens (P24) for HIV and prostate-specific antigen for prostate cancer. The developed devices demonstrate ultralow detection limits at femtomolar to attomolar concentrations with the aid of designed antibodies, aptamers and nanomaterials. Herein, this review presents the sensing mechanisms and biomedical application of various GFET platforms, focusing on their emerging potential as next-generation platforms for rapid, non-invasive and point-of-care diagnostics. Full article

Prostate cancer represents a highly prevalent malignancy affecting men globally, necessitating precise staging and risk stratification for effective patient management. Multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen positron emission tomography (PSMA PET) have individually revolutionized the diagnosis and management of prostate cancer. Recent developments emphasize the integration of these imaging modalities to improve detection capabilities, inform therapeutic interventions, and facilitate personalized management. This narrative article reviews existing literature on the clinical utilization of mpMRI and PSMA PET in prostate cancer. Key areas encompass initial diagnosis, both local and systemic staging, detection of biochemical recurrence, and their influence in treatment strategies. The integration of mpMRI and PSMA PET offers complementary insights, with mpMRI demonstrating superior capability in local tumor characterization and PSMA PET enhancing the detection of nodal and distant metastases. Quantitative imaging biomarkers, including apparent diffusion coefficient (ADC) and standardized uptake values (SUV), have the potential to improve risk stratification and inform personalized treatment strategies. Hybrid imaging techniques may improve diagnostic accuracy and guide decisions regarding surgery, radiotherapy, and systemic treatment. The integration of mpMRI and PSMA PET allows a potentially transformative advancement in the realm of precision imaging for prostate cancer. This integrated approach can improve diagnostic accuracy, better define disease extent, and support personalized management strategies. Full article

Background: Outcomes with enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) are influenced by tumor burden, disease kinetics, and host factors. We evaluated the relative prognostic impact of metastatic pattern, laboratory markers, and prostate-specific antigen (PSA) dynamics in a real-world cohort. Methods: We retrospectively analyzed 72 patients with mCRPC treated with enzalutamide. Progression-Free Survival (PFS) and Overall Survival (OS) were estimated using the Kaplan–Meier method. Multivariate Cox proportional hazards models were utilized to identify independent predictors of survival, incorporating clinical variables (visceral metastases, bone tumor burden), kinetic parameters (Time to Castration Resistance [TTCR], Time to PSA Nadir [TTN]), and host factors (Charlson Comorbidity Index [CCI], Eastern Cooperative Oncology Group Performance Status (ECOG PS), Systemic Immune-Inflammation Index [SII], HALP score). Results: Visceral metastasis was a dominant predictor of poor outcomes, increasing the risk of death by 4.0-fold (HR: 4.05; 95% CI: 1.84–8.89; p < 0.001). A high skeletal tumor burden (≥5 bone lesions) was identified as a critical threshold, associated with a 5.5-fold increase in mortality risk (HR: 5.53; p < 0.001). Delays in initiating enzalutamide significantly compromised survival, with each 1-month delay increasing the risk of death by 7.3% (HR: 1.07; p = 0.003). While early PSA decline (≥50% at 3 months) did not independently predict OS, a prolonged TTN (>12 months) was associated with superior survival. Notably, host-related factors, including age, CCI, and ECOG PS, were not found to be significantly associated with survival outcomes in this specific dataset. Conclusions: Our preliminary findings suggest that survival in real-world mCRPC patients treated with enzalutamide may be influenced predominantly by intrinsic tumor biology—specifically anatomical extent and resistance kinetics—rather than host frailty or comorbidity burden. However, given the retrospective and single-center nature of this study, these findings should be considered hypothesis-generating and require validation in larger, multi-center cohorts. Host-related variables (including age and CCI) were evaluated but were not retained as independent predictors in the final multivariable model. Early initiation of therapy and monitoring of kinetic markers like TTN and TTCR offer superior prognostic stratification compared to static baseline characteristics. Full article

Background: The perioperative period in cancer surgery is characterized by transient metabolic and inflammatory perturbations that may influence early postoperative biochemical dynamics. Surgical stress induces insulin resistance, hyperglycemia, cytokine activation, and metabolic shifts that interact with tumor cell signaling pathways. Intravenous lidocaine has been associated with anti-inflammatory and systemic stabilizing effects beyond analgesia. We investigated whether perioperative lidocaine administration during robotic-assisted radical prostatectomy (RARP) is associated with early postoperative prostate-specific antigen (PSA) dynamics within the context of perioperative metabolic–inflammatory modulation. Methods: In this single-center retrospective cohort study, 180 patients undergoing RARP for localized or locally advanced prostate cancer were stratified according to perioperative intravenous lidocaine exposure. The primary endpoint was undetectable PSA (<0.1 ng/mL) at 6–12 weeks postoperatively. Secondary endpoints included PSA detectability at 3 and 6 months and time to first detectable PSA. Multivariable logistic and Cox regression models were adjusted for established oncologic risk factors. Perioperative glycemic variation, intraoperative lactate dynamics, and postoperative IL-6 levels were analyzed as indicators of stress-induced metabolic activation. Results: Lidocaine exposure was independently associated with higher odds of undetectable PSA at 6–12 weeks (OR 2.10, 95% CI 1.15–3.85) and at subsequent time points. In Cox analysis, lidocaine was associated with a reduced hazard of PSA detectability (HR 0.58, 95% CI 0.37–0.92). Patients receiving lidocaine demonstrated significantly attenuated perioperative hyperglycemia, lower lactate elevation, and reduced IL-6 response. Conclusions: Perioperative intravenous lidocaine administration during RARP was associated with more favorable early PSA dynamics and attenuation of perioperative metabolic–inflammatory activation. Given the retrospective and non-randomized design of the study, these findings should be interpreted as associative and hypothesis-generating, and warrant confirmation in prospective controlled investigations. Full article

The progression of prostate cancer to castration-resistant disease (CRPC) remains a clinical challenge in which oxidative stress intersects with the PI3K/AKT–androgen receptor (AR) axis. Quercetin (QRC) is a redox-active dietary flavonol, yet its mechanistic impact on CRPC is incompletely defined. Here, we tested whether QRC suppresses AR output by directly modulating AKT. C4-2B and 22Rv1 CRPC cell lines were treated with increasing QRC concentrations, with or without enzalutamide (Enz). Proliferation and viability were monitored by IncuCyte imaging and SYTOX Green incorporation. AKT phosphorylation (S473), AR phosphorylation (S210/213), AR abundance and localization, and prostate-specific antigen (PSA) secretion were assessed by immunoblotting, immunofluorescence, and dot blot, respectively. Docking and molecular dynamic simulations were performed to identify and evaluate a putative QRC-binding site on AKT. QRC produced a dose-dependent cytostatic effect (IC₅₀ 24.37 μM in C4-2B; 21.54 μM in 22Rv1) without marked cell death, reduced pAKT(S473) by up to 80%, decreased pAR(S210/213), and diminished nuclear AR and PSA secretion. Simulations suggested a putative druggable allosteric pocket in the AKT1 N-lobe, with G159 emerging as a potential anchor residue. Enz cotreatment with QRC did not produce additive effects, consistent with a model in which QRC acts upstream of ligand-driven AR activation and thereby limits the incremental benefit of AR antagonism under these conditions. These data support QRC as an AKT–AR axis modulator in CRPC and provide a target engagement framework beyond simple ROS scavenging. Full article