In vivo pharmacology

Following the screening process, we subsequently evaluate the activity of the compound in more clinically-relevant tumor models.

Orthotopic & metastatic models

Although orthotopic and metastatic models are more aggressive and difficult to cure, they are more representative of human pathology. Monitoring of these models could be performed through the use of circulating biomarkers (e.g. CEA, CA19.9) or µPET and MRI imaging technologies.

Transgenic & chemo-induced models

In addition to the evaluation of anti-cancer compounds, transgenic and chemo-induced models are used to assess chemo-preventive agents, such as food ingredients. Oncodesign has a number of in-house chemo-induced models, as well as partnerships for the development and breeding of transgenic animals.

Nude rat xenograft models

From a pharmacological and translational research standpoint, Nude rat xenograft models are very relevant for the following reasons, mainly due to their size.

• Enabling easier orthotopic grafting and microsurgery
• More robust and less tolerant to treatment
• Useful for exploring additional routes of administration, such as continuous IV infusion
• Possibility of repetitive biological sampling for PK/PD studies
• Facilitates pharmaco-imaging
• Obtaining preliminary data in the same species in anticipation of regulatory toxicology studies
• Acts as a pharmacological bridge between rodent xenograft models and the clinic

Primary tumor models

Oncodesign has also developed new models of primary tumors generated by using solid tumor samples obtained from volunteers from the anticancer center of Dijon (Georges-François Leclerc Center - CGFL -). The tumor fragments are xenografted in athymic mice after surgical excision and passaged from mice to mice or mice to rats. Remaining fragments from the original human sample are maintained in paraffin and liquid nitrogen in our tumor bank for eventual histological and genetic analyses. Tumor fragments collected from the passages in mice are maintained in our bank for future testing or can be amplified for studies requiring these types of tumors. One of Oncodesign’s R&D axes is the development and the pharmacological and molecular characterization of novel rodent xenograft models. Part of this project is integrated in the CReMEC, hosted in the MEDICEN biocluster in Paris.

Combination studies

Combination studies can be used if an anticancer agent possesses weak activity as a monotherapy or if the activity can be enhanced by combining the agent with standard drugs.

Some considerations to be kept in mind are the following:

• Choice of the drug combination based on mechanism of action
• Choice of the model for a proof-of-concept study or for clinical relevance
• Sequence of the combination
• Toxicity of the combination in order to choose the most appropriate doses of each compound
• Anticancer efficacy of the combination to determine the clinical potential of the combination