Ideal for: AR resistance, weekly blood draws for PSA

VCaP was derived from a vertebral metastatic growth of a prostrate carcinoma. It is a desirable cell line for in vivo studies as it exhibits many of the characteristics of clinical prostate carcinoma. VCaP is a great model to study AR resistance as it expresses AR splice variants that have been shown to drive resistance to AR antagonists (1). Despite these advantages of the VCaP xenograft tumor model, due to the difficult and variable growth in mice between research groups (2), its value is not being applied in vivo. VCaP cells exhibit very poor take rates (<20%) and high growth-rate variability in mice. The take rate would result in the need to inoculate many more animals than the study requires, but even if that approach were taken the growth kinetics are such that an efficacy study could not take place.

In the OncoRat, at 3 weeks post-inoculation, tumor growth permits efficacy studies with a demonstrated 80%+ take rate. VCaP tumors surpass 20,0000 mm3 around 4-5 weeks post inoculation in OncoRat whereas NSG mice show low to no take rate and growth. To establish the VCaP in vivo model for prostate cancer efficacy studies, biomarkers levels were analyzed. AR expression was confirmed via molecular analysis, and PSA in the serum correlated directly with tumor size, with increased levels in the OncoRat due to larger tumors in comparison to NSG mice. The prostatic origin of VCaP tumors was further confirmed via immunohistochemical analyses with both the NSG mice and OncoRat tumors expressed AR and PSA. As expected the VCaP tumor model responded to standard of care agents in the OncoRat.

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Enabling Case Study: VCaP tumor kinetics, characterization and efficacy in the OncoRat

AR expression in VCaP tumors

Drug efficacy in VCaP in OncoRat

  1. European Urology. 2018 Apr;73(4):572-582.
  2. Eskra, J. (2015) Culture methods for VCaP prostate cancer cells

OncoRat VCaP products & services

  • Xenograft efficacy studies, including collection of blood, tissues and tumor for ADME, PK/PD and analysis.
  • Serum collection and the measurement of PSA with a sensitivity of 5ng/ml.
  • Established protocols for castration resistance models
  • Gene expression and histology for biomarkers such as PSA and AR on tumors.
  • Weekly or bi-weekly tumor sampling via fine need aspiration (FNA). For longitudinal evaluation of drug exposure, histology and gene expression.
  • OncoRats off-the-shelf for engraftment at the customers facility.

VCaP tumor serum PSA in OncoRat

Blood was collected prior to inoculation and then weekly after inoculation. Serum was separated and assessed for PSA. Serum PSA is highly correlative with VCaP tumor growth in the OncoRat.

correlation coefficient, r = 0.98

Immunohistochemical analyses of VCaP tumors confirms AR and PSA