Heterotransplant mouse model cohorts of human malignancies: A novel platform for Systematic Preclinical Efficacy Evaluation of Drugs (SPEED)

Advances in molecular biology demonstrate that cancer is heterogeneous disease necessitating a personalized management approach. This is introducing a paradigm shift in clinical trial designs where molecular characterization of cancers is assuming importance equal to ( or even more than) the traditional histologic diagnosis as the eligibility criterion for randomized clinical trials of new therapies. Recommendations have been made to gather the molecular information from clinical phase II trials distinguishing responding from non responding tumors for subsequent planning of large scale phase III trials. However by the time we reach phase II level, more than a billion dollars apart from years of research have been invested. It would be therefore prudent to conceptualize laboratory based platforms to obtain the proof of concept as early as possible, even before embarking upon the pivotal clinical trials. In this regard, we hereby propose and detail a novel preclinical platform incorporating the existing mouse models to address the issue of tumor heterogeneity in a systematic manner through creation of a setting similar to phase II trials in human patients. By providing critical information about a drug's efficacy and the molecular determinants of response early on, this platform would potentially provide a solid foundation to build avant-garde clinical trials integrating recent advances in molecular medicine.