Table 2.

Fundamental goals of the co-clinical trial project

1) Perform co-clinical assessment of novel agents while in phase I/II to permit rapid stratification of responder and resistant populations.
2) Assess single agents or drug combinations in GEM models of genetically distinct and “rarer” cancer types/subsets, in which sizable patient accrual represents a major hurdle.
3) Perform in vivo testing of drug combinations to determine tolerability, efficacy, and pharmacodynamics.
4) Facilitate the prioritization of the most attractive combinations for assessment in humans.
5) Allow the “postclinical” optimization of standard-of-care treatment modalities.
6) Identify mechanisms of acquired resistance to agents/therapeutic modalities (often before clinical trials start).
7) Assess the system impact of agents and combinations (e.g., tumor immune response or impact on tumor stroma and vasculature).
8) Permit the co-clinical and preclinical identification of novel biomarkers.
9) Determine the importance of the temporal sequence of genetic alterations in dictating response or resistance to treatment modalities.