Cancer cell lines and patient derived xenografts (PDX) are commonly engrafted and screened in mouse models of cancer. However, the OncoRat outperforms the mouse as a xenograft model as it is more reliable, efficient & robust. OncoRat consistently demonstrates higher efficiency and more desirable uniformity than mouse tumor model growth profiles. OncoRat is also ideal for downstream analysis as it produces samples ten times larger than mice and is metabolically closer to humans making it the preferred model for efficacy, pharmacokinetics (PK), and toxicology. Hera provides screening services using the OncoRat as well as PDX model services.
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OncoRat efficacy data with standard of care and a collaborator compound (TA-X)

A case study of SRG OncoRat tumor xenografts from a Clinical Cancer Research publication

  • VCaP exhibits many clinical characteristics and is ideal for AR resistance.
  • Very difficult cell line to grow in mice: <20% take rate, highly variable growth profile even with growth matrix such as Matrigel, geltrex and cultrex
  • >90% tumor uptake in OncoRat, more uniform growth for VCaP and MDVR-VCaP
  • Hera provided services to researchers enabling them to:

  • Determine lead compound efficacy towards human prostate tumors
  • Publish research data in a high-impact clinical journal (Clinical Cancer Research)
  • Collect a valuable drug development asset
  • Serial blood draws for biomarker analysis

Serial blood draws & tumor biopsies in OncoRat

Tumor xenografts are limited to a maximum of 10% of the total animal body weight. In mice with body weights topping out at 20-30 grams, the tumors can only grow to 2-3 grams or 2,000-3,000 mm3, limiting the data that investigators can obtain per mouse for molecular analysis, drug exposure and PK/PD, as well as immune cell infiltration. The OncoRat reaches weights of 200-300 grams, permitting tumors in the range of 20,000-30,000 mm3 as well as enough blood for serial draws for biomarker analysis.
This larger size enables serial blood draws, biopsies and Fine Needle Aspirates (FNA) to study tumor and biomarker responses over time in the same animal without significantly effecting tumor kinetics.
In this control study OncoRats bearing MDVR drug resistant VCaP prostate tumors underwent one FNA core sampling weekly for four weeks and four core samplings in week five. The tumor samplings can be prepared and used for molecular analysis, tumor PK/PD, and immune cell infiltration without taking rats out of the study.
Serum PSA was measured using ELISA

Ponnusamy S, He Y, Hwang DJ, Thiyagarajan T, Houtman R, Bocharova V, Sumpter BG, Fernandez E, Johnson D, Du Z, Pfeffer LM, Getzenberg RH, McEwan IJ, Miller DD, Narayanan R. Orally Bioavailable Androgen Receptor Degrader, Potential Next-Generation Therapeutic for Enzalutamide-Resistant Prostate Cancer. Clin Cancer Res. 2019 Sep 3 (on-line).