Prostate最新文献

{"title":"PSA Density and Lesion Volume: Key Factors in Avoiding Unnecessary Biopsies for PI-RADS 3 Lesions.","authors":"Ali Ayranci, Ufuk Caglar, Huseyin Burak Yazili, Feyzi Sinan Erdal, Akif Erbin, Omer Sarilar, Faruk Ozgor","doi":"10.1002/pros.24840","DOIUrl":"10.1002/pros.24840","url":null,"abstract":"<p><strong>Introduction: </strong>The use of multiparametric magnetic resonance imaging (MRI) to guide prostate biopsies has improved cancer detection rates, particularly for high-grade tumors. However, despite guidelines recommending biopsies for lesions with a Prostate Imaging-Reporting and Data System (PI-RADS) score ≥ 3, the clinical significance of PI-RADS 3 lesions remains uncertain. This uncertainty, coupled with the cost and potential complications of biopsies, underscores the need for more accurate risk stratification strategies to avoid unnecessary procedures. Prostate-specific antigen density (PSAD) and index lesion volume are emerging as potential contributors to improve risk assessment.</p><p><strong>Materials and methods: </strong>This was a retrospective analysis of patients who had undergone an MRI-guided transrectal ultrasound (TRUS) prostate biopsy at a tertiary care institution. Patients with PI-RADS 3 lesions were included, and data on demographics, prostate-specific antigens (PSA), PSAD, lesion diameter, and pathology results were collected. The relationships between PSAD, lesion volume, and pathology outcomes were statistically analyzed.</p><p><strong>Results: </strong>Of the 213 patients included, 40 were diagnosed with prostate cancer. PSAD and PSAD x lesion diameter were significantly higher in the patients diagnosed with prostate cancer than those with benign lesions. Among the prostate cancer patients, clinically significant prostate cancer (csPCa) had a higher mean PSAD value than clinically insignificant prostate cancer (cisPCa). ROC analysis found PSAD x lesion diameter to have the highest discriminatory power for detecting csPCa.</p><p><strong>Discussion: </strong>MRI-guided biopsies offer targeted sampling but the clinical significance of PI-RADS 3 lesions remains uncertain. Index lesion volume and PSAD are promising adjunctive markers for risk assessment. Combining these factors could facilitate the avoidance of unnecessary biopsies and improve the detection of csPCa.</p><p><strong>Conclusion: </strong>Incorporating PSAD and index lesion volume into biopsy decision-making may enhance risk stratification, particularly for PI-RADS 3 lesions. Further research is needed to validate these findings and enhance the risk assessment strategies used in making decisions regarding prostate biopsy.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"385-390"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Status of Prostate Biopsy in Africa: Are We Ready for a Targeted Biopsy?","authors":"Ziba Ouima Justin Dieudonne, Kaleab Habtemichae Gebreselassie, Taofiq Olayinka Mohammed, Abdullahi Khalid, Saleh Abdelkerim Nedjim, Anteneh Tadesse Kifle, Marcella D C Biyouma, Hassan Dogo, Christian Agbo, Muhawenimana Emmanuel, Mahamat Ali Mahamat, Ndoye Alain Khassim, Lazarus John, Yameogo Clotaire Alexis Marie Kiemdiba Donega, Mohamed Lezrek, Kirakoya Brahima, Ouattara Adama, Kabore Fasnewende Aristide","doi":"10.1002/pros.24867","DOIUrl":"https://doi.org/10.1002/pros.24867","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer remains a significant public health issue globally, with considerable disparities in diagnostic and management practices, especially in Africa. Traditional diagnostic methods such as transrectal ultrasound-guided biopsies have limitations in accuracy and are associated with potential complications. Emerging targeted biopsy techniques promise improved cancer detection rates and reduced morbidity but face adoption challenges across the African continent due to variable access to advanced imaging technologies and professional expertise.</p><p><strong>Objective: </strong>This study aims to evaluate the current practices of prostate biopsy techniques in Africa, focusing particularly on the readiness for and integration of targeted biopsy methods. It assesses the accessibility, quality, volume of procedures, and availability of advanced diagnostic tools across different regions.</p><p><strong>Results: </strong>The survey included 58 centers across five African regions, representing a 70% response rate from an initial 83 invitations sent. Finger-guided biopsy was the most common method, used by 41 centers, while only one center reported using MRI fusion biopsy. Thirty-five centers routinely administered a rectal enema, and nearly all (n = 50) centers employed antibiotic prophylaxis, predominantly fluoroquinolones. For anesthesia, 12 centers used injectable lidocaine, and 38 centers used intrarectal lidocaine gel. The number of biopsy cores taken varied, with most centers taking 12, while others used fewer.</p><p><strong>Conclusion: </strong>The findings indicate a critical need for concerted efforts to bridge the gap in prostate cancer diagnostics and treatment in Africa. Enhancing the quality of prostate cancer care on the continent requires investments in training, infrastructure, and standardization of practices. Collaborative efforts towards adopting advanced diagnostic tools and methods are essential for aligning African practices with global standards, ultimately improving outcomes for prostate cancer patients.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"e24867"},"PeriodicalIF":2.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to \"Differential Impact of Paired Patient-Derived BPH and Normal Adjacent Stromal Cells on Benign Prostatic Epithelial Cell Growth in 3D Culture\".","authors":"","doi":"10.1002/pros.24864","DOIUrl":"https://doi.org/10.1002/pros.24864","url":null,"abstract":"","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"e24864"},"PeriodicalIF":2.6,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does size matter? A single institution's comparison of Aquablation in prostates greater than or less than 150 mL.","authors":"Renee Ringler, David Gangwish, Paul Horning, Joshua Kuperus, Greg Palmateer, Bernadette M M Zwaans, Jason Hafron, Kenneth M Peters","doi":"10.1002/pros.24810","DOIUrl":"10.1002/pros.24810","url":null,"abstract":"<p><strong>Background: </strong>Surgical management options for lower urinary tract symptoms due to benign prostatic hypertension have remained limited in prostates of large volume. The advent of the Aquablation has created a potential minimally invasive option for treatment in prostates of all volumes. Thus, this study aims to evaluate outcomes and complications of Aquablation in clinical practice based on prostate volume.</p><p><strong>Methods: </strong>Collected variables included adverse events with Clavien-Dindo classifications, transfusion rates, surgical retreatment rates, continued medication use postoperatively, and International Prostate Symptom Score (IPSS) with Quality-of-Life indicator. Aquablations were stratified by preoperative prostate volume.</p><p><strong>Results: </strong>One hundred seventy-four men were included in the study. The average postop decrease in IPSS was 10.28, with a 2.02 point decrease in Quality-of-Life at 1 year. Postop increase in peak urinary flow rate was 7.65 mL/s for an average of 16.44 mL/s. Hemoglobin drop average was 1.78 g/dL, but only 2.3% of patients required a transfusion. 12.9% of patients required surgical retreatment. Six months after Aquablation, 22.9% and 12.9% of patients continued taking Alpha-blockers and Androgen receptor inhibitors, respectively. Adverse events occurred in 33 patients (19.0%). Eighteen patients were excluded from secondary analysis due to unrecorded prostate volume, leaving 123 with volumes <150 mL and 33 with volumes ≥150 mL. Groups were comparable with respect to length of stay, adverse events, blood transfusion, IPSS with Quality-of-Life indicator preoperative and postoperative, postop peak urinary flow, and postop alpha-blocker use. Larger prostates had a higher rate of adverse events, retreatment, postop hemoglobin drop, and postop use of finasteride.</p><p><strong>Conclusions: </strong>Aquablation is a viable treatment option for benign prostatic hyperplasia. Efficacy, safety, subjective outcomes, and adverse event rates were not impacted by prostate volume. However, size does matter as prostates ≥150 mL had higher surgical retreatment rates and postop finasteride use.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"140-147"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of pelvic floor influence on prostate displacement in image-guided radiotherapy.","authors":"Hongbo Chai, Yuya Miyasaka, Yasuhito Hagiwara, Hikaru Souda, Miyu Ishizawa, Hiraku Sato, Takeo Iwai","doi":"10.1002/pros.24808","DOIUrl":"10.1002/pros.24808","url":null,"abstract":"<p><strong>Purpose: </strong>The uncertainty of target location during prostate cancer radiotherapy plays an important role in accurate dose delivery and radiation toxicity in adjacent organs. This study analyzed displacement correlations between the prostate and pelvic floor.</p><p><strong>Methods and materials: </strong>We retrospectively analyzed registration results from 467 daily cone-beam computed tomography (CT) in 12 patients with prostate cancer who received radiation therapy. We analyzed prostate displacement and the pelvic floor relative to the pelvic bone's anatomy in the translational and rotational directions and identified statistical correlations.</p><p><strong>Results: </strong>The systematic (Σ) and random (σ) displacements of the prostate in the three translational directions, anterior-posterior (AP), superior-inferior (SI), and right-left (RL), were 1.49 ± 1.45, 2.10 ± 1.40, and 0.24 ± 0.53 mm, respectively, and in the rotational directions of the pitch, roll, and yaw were 2.10 ± 2.02°, 0.42 ± 0.74°, and 0.42 ± 0.64°, respectively. The pelvic floor displacements were 2.37 ± 1.96, 2.71 ± 2.28, and 0.47 ± 0.84 mm in the AP, SI, and RL directions, respectively, and 0.93 ± 1.49°, 0.98 ± 1.28 °, and 0.87 ± 0.94° in the pitch, roll, and yaw directions, respectively. Additionally, there were statistically significant correlations between the displacement of the prostate and pelvic floor in the AP and SI directions, with correlation coefficients (r) of 0.74 (p < 0.001) and 0.69 (p < 0.001), respectively.</p><p><strong>Conclusions: </strong>The movement of the pelvic floor may be an important factor that causes prostate displacement, affecting the accuracy of radiotherapy. Therefore, it is necessary to take appropriate measures to ensure that the pelvic floor muscle tension is as consistent as possible in the treatment' CT scan and daily treatment.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"123-129"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Life Expectancy in High-Grade Incidental Prostate Cancer Patients Versus Population-Based Controls According to Treatment Type.","authors":"Francesco Di Bello, Letizia Maria Ippolita Jannello, Andrea Baudo, Mario de Angelis, Carolin Siech, Zhe Tian, Jordan A Goyal, Massimiliano Creta, Gianluigi Califano, Giuseppe Celentano, Pietro Acquati, Fred Saad, Shahrokh F Shariat, Luca Carmignani, Ottavio de Cobelli, Alberto Briganti, Felix K H Chun, Nicola Longo, Pierre I Karakiewicz","doi":"10.1002/pros.24816","DOIUrl":"10.1002/pros.24816","url":null,"abstract":"<p><strong>Objective: </strong>To quantify the differences in 5-year overall survival (OS) between high-grade (Gleason sum 8-10) incidental prostate cancer (IPCa) patients and age-matched male population-based controls, according to treatment type: no active versus active treatment.</p><p><strong>Materials and methods: </strong>We relied on the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015) to identify not actively treated and actively treated high-grade IPCa patients. For each case, we simulated an age-matched male control (Monte Carlo simulation), relying on Social Security Administration Life Tables (2004-2020) with 5 years of follow-up. Additionally, we relied on Kaplan-Meier plots to display OS for each treatment type. Multivariable Cox regression models were fitted to predict overall mortality (OM).</p><p><strong>Results: </strong>Of 564 high-grade IPCa patients, 345 (61%) were not actively treated versus 219 (39%) were actively treated, either with radical prostatectomy or radiotherapy. Median OS was 3 years for not actively treated high-grade IPCa patients, with OS difference at 5 years follow-up of 27% relative to their age-matched male population-based controls (37% vs. 64%). Median OS was 8 years for actively treated high-grade IPCa patients, with OS difference at 5 years follow-up of 6% relative to their age-matched male population-based controls (68% vs. 74%). In the multivariable Cox regression model, active treatment independently predicted lower OM (hazard ratio = 0.6; 95% confidence interval = 0.4-0.8; p < 0.001).</p><p><strong>Conclusion: </strong>Relative to Life Tables' derived age-matched male controls, not actively treated high-grade IPCa patients exhibit drastically worse OS than their actively treated counterparts. These observations may encourage clinicians to consider active treatment in newly diagnosed high-grade IPCa patients.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"191-197"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CHARGE: The \"Big Questions\" in Prostate Cancer for 2024.","authors":"Andrea K Miyahira, Howard R Soule, Kenneth J Pienta","doi":"10.1002/pros.24829","DOIUrl":"10.1002/pros.24829","url":null,"abstract":"","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"227-231"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Predictive Factors Analysis of Androgen Deprivation Plus Novel Hormone Therapy as Neoadjuvant Treatment for High-Risk Prostate Cancer.","authors":"Hanyang Tao, Fan Wu, Rui Li, Xinxing Du, Yinjie Zhu, Liang Dong, Jiahua Pan, Baijun Dong, Wei Xue","doi":"10.1002/pros.24817","DOIUrl":"10.1002/pros.24817","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;This investigation explored the clinical features, pathological outcomes, and biochemical recurrence (BCR) duration among high-risk prostate cancer (HRPC) patients who have undergone neoadjuvant therapy (NAT) in combination with radical prostatectomy (RP) and pelvic lymph node dissection (PLND). Additionally, we identified prognostic indicators that discern pathological complete response (pCR) or minimal residual disease (MRD) and BCR.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In total, we examined 76 HRPC patients, who received NAT with either androgen deprivation therapy (ADT) plus apalutamide or ADT plus abiraterone, with subsequent RP and PLND. We conducted a genetic evaluation of patients receiving neoadjuvant apalutamide. Additionally, patient pathological outcomes, circulating prostate-specific antigen (PSA) response rates, and BCR duration were analyzed. Lastly, we employed uni- and multivariate analyses to screen for prognostic factors that govern pCR or MRD and BCR duration.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Patient median age and median PSA at presentation were 69 years (IQR: 66-73), and 47.6 ng/mL (IQR: 24.1-105.75), respectively. We observed marked changes in pCR or MRD rates between the two cohorts. In particular, the ADT plus apalutamide cohort (51.5%) exhibited enhanced rates relative to the ADT plus abiraterone cohort (25.6%) (p = 0.03). The median BCR duration was substantially prolonged among neoadjuvant apalutamide cohort relative to the neoadjuvant abiraterone cohort (261 days vs. 76 days, p = 0.04). Using multivariate analysis, we revealed that the postintervention pre-RP PSA content (≤ 0.1 ng/mL vs. &gt; 0.1 ng/mL) remained a substantial stand-alone indicator of pCR or MRD (odds ratio: 10.712, 95% CI: 2.725-42.105, p &lt; 0.001). Furthermore, supplemental analyses revealed that the ADT plus apalutamide cohort exhibited an augmented serum response rate, which, in turn, reduced the post-intervention pre-RP PSA content. Based on our genetic profiling of the neoadjuvant apalutamide cohort demonstrated high-frequency deleterious changes in the AR axis (30.3%), followed by TP53 mutations (15.15%). Patients with defective AR axis experienced a remarkably shorter median BCR duration relative to patients with other or no genetic alterations (52.5 days vs. 286 and 336 days, respectively, p &lt; 0.0001). Furthermore, using multivariate analysis, we demonstrated that achieving pCR or MRD (hazard ratio [HR]: 0.170, 95% CI: 0.061-0.477, p &lt; 0.001) and presence of defective AR signaling (HR: 11.193, 95% CI: 3.499-35.806, p &lt; 0.001) were strong stand-alone indicators of BCR.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Herein, we demonstrated the superior performance of ADT plus apalutamide in achieving pCR or MRD and in extending BCR duration among HRPC patients. Post-intervention pre-RP PSA content as well as genetic shifts, especially in the AR axis, are critical indicators of patient pathological and clinical outcomes. These findings","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"198-206"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized Medicine: Leave no Patient Behind; Report From the 2024 Coffey-Holden Prostate Cancer Academy Meeting.","authors":"Andrea K Miyahira, Marina Sharifi, Lisa N Chesner, Asmaa El-Kenawi, Roni Haas, Laura A Sena, Alok K Tewari, Kenneth J Pienta, Howard R Soule","doi":"10.1002/pros.24826","DOIUrl":"10.1002/pros.24826","url":null,"abstract":"<p><strong>Introduction: </strong>The 11th Annual 2024 Coffey - Holden Prostate Cancer Academy (CHPCA) Meeting, was themed \"Personalized Medicine: Leave No Patient Behind,\" and was held from June 20 to 23, 2024 at the University of California, Los Angeles, Luskin Conference Center, in Los Angeles, CA.</p><p><strong>Methods: </strong>The CHPCA Meeting is an academy-styled annual conference organized by the Prostate Cancer Foundation, to focus discussion on the most critical emerging research that have the greatest potential to advance knowledge of prostate cancer biology and treatment. The 2024 CHPCA Meeting was attended by 75 academic investigators and included 37 talks across 8 sessions.</p><p><strong>Results: </strong>The meeting sessions focused on: novel human, mouse and systems biology research models, novel immunotherapies for prostate cancer, efforts to overcome treatment resistance, the role of metabolism and diet in prostate cancer biology and as a therapeutic target, mechanisms that drive differentiation into neuroendocrine cancer subtypes, the evolving prostate cancer epigenome in disease progression and treatment resistance, and machine learning and advanced computational approaches for precision oncology.</p><p><strong>Discussion: </strong>This article summarizes the presentations and discussions from the 2024 CHPCA Meeting. We hope that sharing this knowledge will inspire and accelerate research into new discoveries and solutions for prostate cancer.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"211-226"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein kinase D1 mitigation against etoposide induced DNA damage in prostate cancer is associated with increased α-Catenin.","authors":"Sanjeev Shukla, Teruko Osumi, Mohammed Al-Toubat, Samuel Serrano, Pankaj Kumar Singh, Mario Mietzsch, Robert McKenna, Jonathan Chardon-Robles, Sunil Krishnan, K C Balaji","doi":"10.1002/pros.24812","DOIUrl":"10.1002/pros.24812","url":null,"abstract":"<p><strong>Background: </strong>The E-cadherin, α- and β-Catenin interaction at the cell adherens junction plays a key role in cell adhesion; alteration in the expression and function of these genes are associated with disease progression in several solid tumors including prostate cancer. The membranous β-Catenin is dynamically linked to the cellular cytoskeleton through interaction with α-Catenin at amino acid positions threonine 120 (T120) to 151 of β-Catenin. Nuclear presence of α-Catenin modulates the sensitivity of cells to DNA damage. The objective of this study is to determine the role of α-Catenin and protein kinase D1 (PrKD1) in DNA damage response.</p><p><strong>Methods: </strong>Prostate cancer cells; LNCaP, LNCaP (Sh-PrKD1; silenced PrKD1), C4-2 and C4-2 PrKD1 were used for various sets of experiments to determine the role of DNA damage in PrKD1 overexpression and silencing cells. These cells were treated with compound-10 (100 nM) and Etoposide (30 µM), total cell lysates, cytosolic and nuclear fractions were prepared to observe various protein expressions. We performed single cell gel electrophoresis (COMET assay) to determine the etoposide induce DNA damage in C4-2 and C4-2 PrKD1 cells. The animal experiments were carried out to determine the tolerability of compound-10 by mice and generate preliminary data on efficacy of compound-10 in modulating the α-Catenin and PrKD1 expressions in inhibiting tumor progression.</p><p><strong>Results: </strong>PrKD1, a novel serine threonine kinase, phosphorylates β-Catenin T120. In silico analysis, confirmed that T120 phosphorylation alters β- to α-Catenin binding. Forced expression of PrKD1 in prostate cancer cells increased β- and α-Catenin protein levels associated with reduced etoposide induced DNA damage. Downregulation of α-Catenin abrogates the PrKD1 mitigation of DNA damage. The in vitro results were corroborated in vivo using mouse prostate cancer patient derived xenograft model by inhibition of PrKD1 kinase activity with compound-10, a selective PrKD inhibitor, demonstrating decreased total β- and α-Catenin protein levels, and β-Catenin T120 phosphorylation.</p><p><strong>Conclusions: </strong>Alteration in DNA damage response pathways play major role in prostate cancer progression. The study identifies a novel mechanism of α-Catenin dependent DNA damage mitigation role for PrKD1 in prostate cancer.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"156-164"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}