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Updated: Apr 6, 2026
Pre-clinical Orthotopic Murine Model of Human Prostate Cancer
Published on: August 29, 2016
Multimodal imaging guided preclinical trials of vascular targeting in prostate cancer
James Kalmuk1,2, Margaret Folaron1,3, Julian Buchinger1,4
1Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA.
Abstract:
The high mortality rate associated with castration-resistant prostate cancer (CRPC) underscores the need for improving therapeutic options for this patient population. The purpose of this study was to examine the potential of vascular targeting in prostate cancer. Experimental studies were carried out in subcutaneous and orthotopic Myc-CaP prostate tumors implanted into male FVB mice to examine the efficacy of a novel microtubule targeted vascular disrupting agent (VDA), EPC2407 (Crolibulin™). A non-invasive multimodality imaging approach based on magnetic resonance imaging (MRI), bioluminescence imaging (BLI), and ultrasound (US) was utilized to guide preclinical trial design and monitor tumor response to therapy. Imaging results were correlated with histopathologic assessment, tumor growth and survival analysis. Contrast-enhanced MRI revealed potent antivascular activity of EPC2407 against subcutaneous and orthotopic Myc-CaP tumors. Longitudinal BLI of Myc-CaP tumors expressing luciferase under the androgen response element (Myc-CaP/ARE-luc) revealed changes in AR signaling and reduction in intratumoral delivery of luciferin substrate following castration suggestive of reduced blood flow. This reduction in blood flow was validated by US and MRI. Combination treatment resulted in sustained vascular suppression, inhibition of tumor regrowth and conferred a survival benefit in both models. These results demonstrate the therapeutic potential of vascular targeting in combination with androgen deprivation against prostate cancer.
Insights
Vascular targeting with Crolibulin™ shows promise for castration-resistant prostate cancer (CRPC). Combining this vascular disrupting agent (VDA) with androgen deprivation therapy significantly improved survival in preclinical models.
Area of Science:
- Oncology
- Vascular Biology
- Preclinical Research
Background:
- Castration-resistant prostate cancer (CRPC) has a high mortality rate, necessitating novel therapeutic strategies.
- Vascular targeting presents a potential approach to treat prostate cancer by disrupting tumor blood supply.
Purpose of the Study:
- To evaluate the efficacy of a novel vascular disrupting agent (VDA), EPC2407 (Crolibulin™), in prostate cancer models.
- To assess the potential of combining vascular targeting with androgen deprivation therapy for CRPC.
Main Methods:
- Experimental studies utilized subcutaneous and orthotopic Myc-CaP prostate tumor models in FVB mice.
- A multimodality non-invasive imaging approach (MRI, BLI, US) was employed for therapy monitoring.
- Tumor response was assessed via imaging, histopathology, tumor growth, and survival analysis.
Main Results:
- EPC2407 demonstrated potent antivascular activity in both subcutaneous and orthotopic Myc-CaP tumors.
- Castration led to reduced blood flow in tumors, confirmed by BLI, US, and MRI.
- Combination treatment with EPC2407 and androgen deprivation resulted in sustained vascular suppression, inhibited tumor regrowth, and improved survival.
Conclusions:
- Vascular targeting with EPC2407 is a promising strategy for prostate cancer treatment.
- Combining vascular disrupting agents with androgen deprivation therapy offers a survival benefit in preclinical prostate cancer models.
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