Mouse models of cancer have been used in discovery research for several decades now. The mouse models that are used most frequently to qualify new anti-cancer drugs for study in human clinical trials have been xenografts of human tumors transplanted into immunodeficient mice. However, the selection of the optimal tumor model type, appropriate formulation, dosing regimen, or drug combination remains a challenge. In addition, every tumor model study typically assesses several study endpoints, the most common endpoints are:
- Log-cell kill (LCK)
- Tumor growth inhibition (TGI)
- Rate of tumor growth or tumor delay
- Metastasis or metastatic growth rate
- Histopathologic end points
- Immunohistochemistry endpoints
Additional endpoints such as the analysis of pharmacodynamic biomarkers can be added depending on the needs of the project and the nature of the compound.
Cephrim Biosciences has extensive expertise in oncology and will support its clients with the selection of the optimal tumor model, protocol design and in the selection of appropriate endpoints to maximize the value that can be obtained from each study.
We offer a broad selection of well-established human and murine tumor xenografts that can be used in the evaluation of anticancer drugs that act as general anti-neoplastic or anti-angiogenesis agents, immune system stimulators or targeted drugs with a defined mode-of-action.
Human tumor xenograft models available at Cephrim Biosciences
- Head & Neck
- Blood/lymphoma/myeloid tumors
Syngeneic mouse tumor models are also available for specific applications
- Lung: Lewis lung carcinoma
- B-cell lymphoma: B16F1
- Renal cancer: Renca
In addition, we offer testing of potential anti-angiogenic therapies using metronomic dosing, which requires long term, low-level dosing to inhibit the growth and development of the vascular endothelium while avoiding whole-animal toxicity. As a quick assay for infiltration of host cells and the formation of new blood vessels in vivo we currently offer the Matrigel plug assay.
The analysis of pharmacodynamic biomarkers is now frequently included in the design of early rodent xenograft studies. Especially the effects of targeted cancer drugs with defined mode-of-action can be tracked as changes to specific phosphoprotein signaling events or as alterations in gene expression profiles. The analysis of biomarkers therefore provides additional study end-points that can be important for the final selection of the optimal lead candidate, and represents an attractive add-on parameter in standard xenograft studies. Cephrim Biosiences has wide-ranging experience in the analysis of biomarkers and offers its clients support in model selection, study design and data analysis.
- Tumor model selection for optimal target expression
- Tumor profiling for target expression and modulation (e.g. target gene- and/or protein expression, phosphoprotein analysis, surrogate markers, cytokine levels, etc.)
- Tumor or host tissue sampling throughout the preclinical study to monitor for target modulation