PD35-02 CBP-1018, A DUAL-LIGAND DRUG TARGETING PSMA-FOLR1, IS AVAILABLE FOR PROSTATE CANCER TREATMENT AND HAS THE POTENTIAL TO BE USED IN COMBINATION WITH OTHER THERAPIES

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology III (PD35)1 May 2024PD35-02 CBP-1018, A DUAL-LIGAND DRUG TARGETING PSMA-FOLR1, IS AVAILABLE FOR PROSTATE CANCER TREATMENT AND HAS THE POTENTIAL TO BE USED IN COMBINATION WITH OTHER THERAPIES Ruilin Zhuang and Hai Huang Ruilin ZhuangRuilin Zhuang and Hai HuangHai Huang View All Author Informationhttps://doi.org/10.1097/01.JU.0001009396.21455.74.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The aim of this study was to further validate the potent antitumor effect of CBP-1018 in ex vivo experiments and to investigate its potential value in combination with other clinical drugs, so as to provide new therapeutic drugs and strategies for prostate cancer treatment. METHODS: We verified the expression and prognostic relevance of PSMA and FOLR1 in prostate cancer by immunohistochemical staining, immunofluorescence co-localization, RT-PCR, Western Blot, and bioinformatics techniques, verified the antitumor effect of CBP-1018 and compared it with the piggyback drug alone by CCK8 cell activity assay, in vivo experiments in nude mice, and immunohistochemical staining. MMAE, validate the anti-tumor mechanism of CBP-1018 by flow cytometry to detect apoptosis, cycle, etc., use adenovirus to construct PSMA and FOLR1 overexpression cell lines to validate the correlation between the ligand expression and the anti-tumor activity of the drugs, and explore the synergistic effect of CBP-1018 with prostate cancer by CCK8 cell activity assay and CalcuSyn calculation of synergistic index (CI). synergistic effects of conventional therapeutic drugs. RESULTS: Our study found that PSMA1 and FOLR1 were both significantly highly expressed in prostate cancer, with significant correlation with clinical stage and survival prognosis of prostate cancer, and co-expression phenomenon. Experiments showed that CBP-1018 produced significant anti-tumor effects in a variety of prostate cancer cell lines and in vivo models, and the effect was better than its piggybacking naked drug MMAE. Further studies revealed that CBP-1018 exerted its anti-tumor effects mainly by releasing MMAE, which binds to microtubules and stalls the cellular differentiation cycle in the G2/M phase, and then induces cell apoptosis. Meanwhile, we found that CBP-1018 showed more efficient antitumor effects when combined with enzalutamide and docetaxel. CONCLUSIONS: Our results demonstrated that CBP-1018 is a dual-targeted ligand drug that can be used in prostate cancer treatment, has significant ex vivo and ex vivo anti-tumor effects, and can be combined with other prostate cancer therapeutic agents to produce stronger anti-tumor effects, which provides a new drug option and therapeutic strategy for the treatment of prostate cancer. Source of Funding: N/A © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e725 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Ruilin Zhuang More articles by this author Hai Huang More articles by this author Expand All Advertisement PDF downloadLoading ...