B7-H3-liquid biopsy for the characterization and monitoring of the dynamic biology of prostate cancer Journal Article
| Authors: | Ju, Y.; Watson, J.; Wang, J. J.; Yen, Y. T.; Gevorkian, L.; Chen, Z.; Tu, K. H.; Salumbides, B.; Phung, A.; Zhao, C.; Kim, H.; Ji, Y. R.; Zhang, R. Y.; Lee, J.; Gong, J.; Scher, K.; You, S.; Chen, J. F.; Tseng, H. R.; Zhu, Y.; Posadas, E. M. |
| Article Title: | B7-H3-liquid biopsy for the characterization and monitoring of the dynamic biology of prostate cancer |
| Abstract: | Background: B7-H3 is a promising target for cancer therapy, notably in prostate cancer (PCa), particularly in metastatic, castration-resistant PCa (mCRPC). With the development of B7-H3-targeted therapies, there is a need for a rapid, reliable, and cost-effective method to detect and monitor B7-H3 expression. Leveraging their abundance and stability, we developed a liquid biopsy assay using extracellular vesicles (EVs) for this purpose. Methods: B7-H3+ EVs were isolated using a B7-H3 antibody-mediated, click chemistry-based enrichment method. Antibodies were conjugated to methyltetrazine-grafted microbeads. EVs were isolated from 100 μL of plasma from metastatic, castration-sensitive PCa (mCSPC) (n = 43) and mCRPC (n = 103) patients and quantified using RT-qPCR of ACTB. Measurements were compared with the patient's disease status over time. Results: The assay detected higher B7-H3+ EVs in mCRPC than mCSPC and increased when mCSPC transitioned to mCRPC. Elevated B7-H3+ EVs were associated with lower overall survival (Hazard ratio (HR) 2.19, p = 0.01). In patients with serial plasma samples, B7-H3+ EV levels reflected treatment response and disease progression. Conclusions: This B7-H3+ EV assay represents a significant advancement in utilizing tumor-derived EVs for a non-invasive, quantitative, and consistent real-time measurement of B7-H3. This assay warrants further development as a companion diagnostic for B7-H3 targeted therapies in PCa and other conditions. © 2025 Elsevier Ltd |
| Keywords: | adult; controlled study; treatment response; human cell; major clinical study; overall survival; computer assisted tomography; gene expression; clinical assessment; cancer therapy; prostate cancer; cost effectiveness analysis; clinical study; immunocytochemistry; quantitative analysis; membrane protein; nanoparticle; real time polymerase chain reaction; disease exacerbation; antibody; click chemistry; exosome; antibody conjugate; gene expression level; diagnostics; immunogold staining; gold nanoparticle; human; male; article; metastatic castration resistant prostate cancer; lncap cell line; extracellular vesicles; liquid biopsy; 22rv1 cell line; metastatic castration sensitive prostate cancer; real time reverse transcription polymerase chain reaction |
| Journal Title: | Drug Resistance Updates |
| Volume: | 79 |
| ISSN: | 1368-7646 |
| Publisher: | Harcourt Publishers Ltd |
| Date Published: | 2025-03-01 |
| Start Page: | 101207 |
| Language: | English |
| DOI: | 10.1016/j.drup.2025.101207 |
| PROVIDER: | scopus |
| PUBMED: | 39914189 |
| DOI/URL: | |
| Notes: | Article -- MSK corresponding author is Jie-Fu Chen -- Source: Scopus |
