Recent advances in antibody-drug conjugates for metastatic castration-resistant prostate cancer.
10.3724/zdxbyxb-2025-0391
- Author:
Jiacheng XU
1
;
Yutao MA
2
;
Pengcheng HU
2
;
Jiatao YAO
2
;
Haichao CHEN
3
;
Qi MA
4
Author Information
1. Health Science Center, Ningbo University, Ningbo 315211, Zhejiang Province, China. 873511464@qq.com.
2. Health Science Center, Ningbo University, Ningbo 315211, Zhejiang Province, China.
3. Department of Urology, the First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China. nbdxchc@sina.com.
4. Comprehensive Genitourinary Cancer Center, the First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China. fyymaqi@nbu.edu.cn.
- Publication Type:English Abstract
- Keywords:
Antibody-drug conjugate;
Metastatic castration-resistant prostate cancer;
Review;
Target antigen
- MeSH:
Humans;
Prostatic Neoplasms, Castration-Resistant/pathology*;
Male;
Immunoconjugates/therapeutic use*;
Glutamate Carboxypeptidase II/immunology*;
Antibodies, Monoclonal, Humanized/therapeutic use*;
B7 Antigens/immunology*;
Neoplasm Metastasis;
Prostate-Specific Antigen;
Antigens, Neoplasm/immunology*;
Antigens, Surface;
Camptothecin/analogs & derivatives*;
Oxidoreductases
- From:
Journal of Zhejiang University. Medical sciences
2025;54(5):685-693
- CountryChina
- Language:Chinese
-
Abstract:
Patients with metastatic castration-resistant prostate cancer (mCRPC) face poor prognoses due to tumor heterogeneity and drug resistance. Antibody-drug conjugates (ADCs) have been under development for over two decades for mCRPC treatment. Several clinical trials have demonstrated promising antitumor activity and acceptable safety profiles for ADCs in this setting. Among prostate-specific membrane antigen (PSMA)-targeted ADCs, ARX517 demonstrates superior safety and more significant prostate-specific antigen (PSA) reductions compared to earlier agents such as MLN2704, PSMA-ADC, and MEDI3726. ADCs targeting B7-H3, such as MGC018 and DB-1311, have also shown antitumor activity. ADCs targeting other antigens, including six-transmembrane epithelial antigen of the prostate (STEAP)1 (DSTP3086S), trophoblast cell surface antigen (TROP)2 (sacituzumab govitecan), and solute carrier (SLC) 44A4 (ASG-5ME), have shown preliminary antitumor activity in early trials but face challenges with insufficient efficacy or toxicity. Tisotumab vedotin (targeting tissue factor) has shown no significant therapeutic response in mCRPC. Meanwhile, disitamab vedotin (HER2-targeted), ABBV-969 and DXC008 (both dual PSMA/STEAP1-targeted) are currently under evaluation. Notably, an international multicenter phase Ⅲ clinical trial (NCT06925737) for mCRPC has been initiated in May 2025 for evaluating B7-H3-targeted ADC ifinatamab deruxtecan. This review summarizes recent advances in ADCs targeting key antigens in mCRPC (including PSMA, B7-H3, STEAP1, TROP2, SLC44A4, and others) and explores combination strategies, offering insights to inform the clinical management of mCRPC.
