PQ - 17 Since current methods to assess potential cancer treatments are cumbersome, expensive, and often inaccurate, can we develop other methods to rapidly test interventions for cancer treatment or prevention? Background: There are no reliable models that predict drug response in human tumors. Tumor cells in culture are widely used to help identify and characterize potential drug targets, and they can serve as useful models to check initial drug penetration of cell membranes and target engagement. Mouse xenograft or genetically engineered mouse models often provide good settings to test drug pharmacodynamics, but seldom yield reliable measures of drug efficacy. Other animal models are used extensively for drug pharmacokinetic tests, but none of these models are useful mimics of drug activity in humans. This Provocative Question calls for the development and testing of new systems that accurately predict how drugs will act in humans. Feasibility: Advances in 3-dimensional cell culture suggest that multiple cell types can be assembled in vitro and that engineered tissues often mimic many of the features of human organs. If systems can be developed that mimic the natural environment of tumors, perhaps these models will recapitulate drug action. It also seems possible that complex cell-free systems could be developed that would recapitulate at least some features of drug responses. Since it seems unlikely that any one new system will serve as an accurate model for all tumors, each may need to be tuned to the particular features of a particular tumor type or subtype. Implications of success: If systems can be developed that accurately predict drug responses in human, advances in drug treatment or prevention would be dramatically streamlined, and the time frame for drug development shortened considerably. These new systems might also allow strategies for combination therapies to advance from empirical tests to approaches that are based on the biology of the tumor and its environment. The ultimate benefit for patients would be immense. |
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