Mp41-19 Assessing Adc Targets Expression and Predictive Clinical Indicators in Metastatic Castration-Resistant Prostate Cancer

You have accessJournal of UrologyProstate Cancer: Markers I (MP41)1 May 2024MP41-19 ASSESSING ADC TARGETS EXPRESSION AND PREDICTIVE CLINICAL INDICATORS IN METASTATIC CASTRATION-RESISTANT PROSTATE CANCER Yelin Mulati, Yuxuan Tian, Qi Shen, Yu Fan, Qian Zhang, and Zhisong He Yelin MulatiYelin Mulati , Yuxuan TianYuxuan Tian , Qi ShenQi Shen , Yu FanYu Fan , Qian ZhangQian Zhang , and Zhisong HeZhisong He View All Author Informationhttps://doi.org/10.1097/01.JU.0001008896.93851.5b.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Metastatic castration-resistant prostate cancer (mCRPC) poses clinical challenges with sparse treatments and sample acquisition issues. Antibody-drug conjugates (ADCs) offer cancer treatment potential, where target expression is pivotal. This study aims to investigate the influence of therapeutic drug-induced stress on ADC target expression in prostate cancer (PCa) and to explore the utility of clinically available indicators in predicting ADC target expression in mCRPC. METHODS: Paired paraffin samples from 17 patients at Peking University First Hospital from 2013 to 2022 were retrospectively collected. These pairs included prostate biopsy samples (PB) from de novo PCa (dnPCa) and bone metastatic lesions (BML) from mCRPC consecutively. Drug history records were complete. All samples were successively sectioned to allow comparative analysis. Immunohistochemistry assessed the expression of 6 targets: HER2, TROP2, NECTIN4, STEAP1, B7H3 and PSMA, with positive expression defined as tumor cell membrane staining of ++/+++. RESULTS: After treatment of docetaxel (Doc) or abiraterone (Abi), STEAP1, B7H3, and PSMA maintained high expression levels, while NECTIN4 exhibited significantly reduced expression. Patients treated with Doc experienced a increase in HER2 expression (p=0.033) and a decrease in TROP2 (p=0.004), whereas those treated with Abi showed an increase in STEAP1 expression (p=0.089). HER2 expression in mCRPC was associated with initial tPSA >200 ng/dL (p=0.076), and HER2 expression was associated with B7H3 status in the prostate biopsy sample from dnPCa (p=0.025). Furthermore, HER2 expression status in mCRPC could be predicted using inital tPSA, previous Doc treatment status, and the expression status of HER2 or B7H3 from the initial prostate biopsy sample (AUC=0.89). CONCLUSIONS: STEAP1, B7H3 and PSMA may be potential therapeutic targets for mCRPC after single or multiple lines of treatments. Doc or Abi-induced stress exhibited effects on target expressions, showing the dynamic nature of ADC target profiles in response to therapeutic interventions. HER2 expression status in mCRPC can be predicted using clinical indicators like tPSA, Doc using history, HER and B7H3 expression status from initial prostate biopsy. Download PPT Source of Funding: National High Level Hospital Clinical Research Funding (Interdepartmental Clinical Research Project of Peking University First Hospital), 23cz020301-4802093 © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e682 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Yelin Mulati More articles by this author Yuxuan Tian More articles by this author Qi Shen More articles by this author Yu Fan More articles by this author Qian Zhang More articles by this author Zhisong He More articles by this author Expand All Advertisement PDF downloadLoading ...