Prostate-Specific Membrane Antigen-Targeted Antibody–Drug Conjugates: A Promising Approach for Metastatic Castration-Resistant Prostate Cancer

Prostate cancer (PCa), especially metastatic castration-resistant prostate cancer (mCRPC), is a significant cancer characterized by its poor prognosis and limited treatment options. Prostate-specific membrane antigen (PSMA) has emerged as a diagnostic and therapeutic target for PCa due to its restri...

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Main Authors: Chia-Hsien Shih, Tzuo-Yi Hsieh, Wen-Wei Sung
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/7/513
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author Chia-Hsien Shih
Tzuo-Yi Hsieh
Wen-Wei Sung
author_facet Chia-Hsien Shih
Tzuo-Yi Hsieh
Wen-Wei Sung
author_sort Chia-Hsien Shih
collection DOAJ
description Prostate cancer (PCa), especially metastatic castration-resistant prostate cancer (mCRPC), is a significant cancer characterized by its poor prognosis and limited treatment options. Prostate-specific membrane antigen (PSMA) has emerged as a diagnostic and therapeutic target for PCa due to its restricted expression in malignant prostate tissues. In this case, several PSMA-targeting molecules were developed for radiotherapy and immunotherapy. Antibody–drug conjugates (ADCs) are a novel therapeutic approach for various carcinomas that can selectively target PSMA-positive tumor cells and minimize off-target toxicity. ADCs have made great progress in the treatment of breast and bladder cancers, and some have received FDA approval for target therapy. However, studies on PSMA ADCs are limited, and most clinical trials are at stage I or II. Therefore, this study reviewed trials about PSMA-targeting ADCs for the treatment of PCa. Clinical trials have reported a favorable pharmacokinetic profile and antitumor activity. Toxicity studies have revealed manageable adverse effects, with no significant off-target toxicity in PSMA-negative tissues. This study highlights the therapeutic potential of PSMA ADCs for the treatment of mCRPC. However, it also emphasizes the necessity of further clinical investigation to optimize efficacy, safety, and patient outcomes.
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spelling doaj-art-7bccbca369f44e7a8314c246584bf3e62025-08-20T03:08:46ZengMDPI AGCells2073-44092025-03-0114751310.3390/cells14070513Prostate-Specific Membrane Antigen-Targeted Antibody–Drug Conjugates: A Promising Approach for Metastatic Castration-Resistant Prostate CancerChia-Hsien Shih0Tzuo-Yi Hsieh1Wen-Wei Sung2School of Medicine, Chung Shan Medical University, Taichung 40201, TaiwanSchool of Medicine, Chung Shan Medical University, Taichung 40201, TaiwanSchool of Medicine, Chung Shan Medical University, Taichung 40201, TaiwanProstate cancer (PCa), especially metastatic castration-resistant prostate cancer (mCRPC), is a significant cancer characterized by its poor prognosis and limited treatment options. Prostate-specific membrane antigen (PSMA) has emerged as a diagnostic and therapeutic target for PCa due to its restricted expression in malignant prostate tissues. In this case, several PSMA-targeting molecules were developed for radiotherapy and immunotherapy. Antibody–drug conjugates (ADCs) are a novel therapeutic approach for various carcinomas that can selectively target PSMA-positive tumor cells and minimize off-target toxicity. ADCs have made great progress in the treatment of breast and bladder cancers, and some have received FDA approval for target therapy. However, studies on PSMA ADCs are limited, and most clinical trials are at stage I or II. Therefore, this study reviewed trials about PSMA-targeting ADCs for the treatment of PCa. Clinical trials have reported a favorable pharmacokinetic profile and antitumor activity. Toxicity studies have revealed manageable adverse effects, with no significant off-target toxicity in PSMA-negative tissues. This study highlights the therapeutic potential of PSMA ADCs for the treatment of mCRPC. However, it also emphasizes the necessity of further clinical investigation to optimize efficacy, safety, and patient outcomes.https://www.mdpi.com/2073-4409/14/7/513prostate neoplasmmetastasistarget therapychemotherapysystemic therapy
spellingShingle Chia-Hsien Shih
Tzuo-Yi Hsieh
Wen-Wei Sung
Prostate-Specific Membrane Antigen-Targeted Antibody–Drug Conjugates: A Promising Approach for Metastatic Castration-Resistant Prostate Cancer
Cells
prostate neoplasm
metastasis
target therapy
chemotherapy
systemic therapy
title Prostate-Specific Membrane Antigen-Targeted Antibody–Drug Conjugates: A Promising Approach for Metastatic Castration-Resistant Prostate Cancer
title_full Prostate-Specific Membrane Antigen-Targeted Antibody–Drug Conjugates: A Promising Approach for Metastatic Castration-Resistant Prostate Cancer
title_fullStr Prostate-Specific Membrane Antigen-Targeted Antibody–Drug Conjugates: A Promising Approach for Metastatic Castration-Resistant Prostate Cancer
title_full_unstemmed Prostate-Specific Membrane Antigen-Targeted Antibody–Drug Conjugates: A Promising Approach for Metastatic Castration-Resistant Prostate Cancer
title_short Prostate-Specific Membrane Antigen-Targeted Antibody–Drug Conjugates: A Promising Approach for Metastatic Castration-Resistant Prostate Cancer
title_sort prostate specific membrane antigen targeted antibody drug conjugates a promising approach for metastatic castration resistant prostate cancer
topic prostate neoplasm
metastasis
target therapy
chemotherapy
systemic therapy
url https://www.mdpi.com/2073-4409/14/7/513
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AT tzuoyihsieh prostatespecificmembraneantigentargetedantibodydrugconjugatesapromisingapproachformetastaticcastrationresistantprostatecancer
AT wenweisung prostatespecificmembraneantigentargetedantibodydrugconjugatesapromisingapproachformetastaticcastrationresistantprostatecancer