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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
[Recent advances in antibody-drug conjugates for metastatic castration-resistant prostate cancer]
Jiacheng Xu1, Yutao Ma2, Pengcheng Hu2
1Health Science Center, Ningbo University, Ningbo 315211, Zhejiang Province, China. 873511464@qq.com.
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.
Insights
Antibody-drug conjugates (ADCs) show promise for treating metastatic castration-resistant prostate cancer (mCRPC). Newer agents targeting PSMA and B7-H3 antigens demonstrate improved efficacy and safety, with ongoing trials exploring combination strategies.
Area of Science:
- Oncology
- Pharmacology
- Cancer Therapeutics
Background:
- Metastatic castration-resistant prostate cancer (mCRPC) presents significant treatment challenges due to tumor heterogeneity and drug resistance.
- Antibody-drug conjugates (ADCs) have emerged as a promising therapeutic strategy for mCRPC over the past two decades.
- Several ADCs have demonstrated notable antitumor activity and acceptable safety profiles in clinical trials for mCRPC.
Purpose of the Study:
- To review recent advancements in antibody-drug conjugates (ADCs) for metastatic castration-resistant prostate cancer (mCRPC) treatment.
- To summarize the efficacy and safety of ADCs targeting various antigens, including PSMA, B7-H3, STEAP1, TROP2, and SLC44A4.
- To explore potential combination strategies involving ADCs for improved mCRPC management.
Main Methods:
- Comprehensive literature review of clinical trials and preclinical studies on ADCs in mCRPC.
- Analysis of ADC efficacy, safety, and antigen targeting in the context of prostate cancer.
- Evaluation of emerging ADC candidates and combination therapeutic approaches.
Main Results:
- Prostate-specific membrane antigen (PSMA)-targeted ADCs like ARX517 show superior safety and PSA reduction compared to earlier agents.
- B7-H3-targeted ADCs (e.g., MGC018, DB-1311) exhibit antitumor activity; ifinatamab deruxtecan is in a Phase III trial.
- ADCs targeting STEAP1, TROP2, and SLC44A4 show preliminary activity but face challenges with efficacy or toxicity.
Conclusions:
- ADCs targeting key antigens represent a significant advancement in mCRPC therapy.
- Ongoing research and clinical trials are refining ADC efficacy and safety profiles.
- Combination strategies hold potential for enhancing therapeutic outcomes in mCRPC.
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