aPL Cure aS the Foundation oF the Co-CLiniCaL triaL ProJeCt

The “co-clinical trial” project stems from the realization of the tremendous power of preclinical testing of new drugs and drug combinations in faithful genetically engineered mouse (GEM) models of human cancer. A “GEM to human” or “preclinical to clinical” approach has already proven to be highly effective toward the eradication of a subset of diseases [e.g., acute promyelocytic leukemia (APL)] in which the genetic defects are defined and “druggable” targets and targeted therapies have been identified. In this article, we discuss how we propose to export this paradigm for the optimization of therapy in other tumor types, and in principle to any disease, using the more refined GEM models and more sophisticated modeling capability currently available. We review how the co-clinical trial project is aimed at overcoming four fundamental challenges to making the use of preclinical models transformative in the real-time design of effective and informative clinical trials and ultimately, disease eradication: