title: The APL paradigm and the "co-clinical trial" project.
abstract: Tremendous advances in technologies have allowed the attainment of powerful insights into the molecular and genetic determinants that drive human cancers. However, this acquired knowledge has been translated into effective therapeutics very slowly, in part due to difficulty in predicting which drug or drug combination is likely to be effective in the complex mutational background of human cancers. To address this difficulty we have proposed and initiated the "co-clinical trial" project, in which we exploit mouse models that faithfully replicate the variety of mutational events observed in human cancers, to conduct preclinical trials that parallel ongoing human phase I/II clinical trials. Here, we focus on concepts relevant to the application of this novel paradigm and the essential components required for its implementation to ultimately achieve the rational and rapid development of new therapeutic treatments.
authors: Cancer Genetics Program, Division of Genetics, Department of Medicine and Pathology, Beth Israel Deaconess Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors: Caterina
authors: C
authors: Nardella
authors: Andrea
authors: A
authors: Lunardi
authors: Akash
authors: A
authors: Patnaik
authors: Lewis C
authors: LC
authors: Cantley
authors: Pier Paolo
authors: PP
authors: Pandolfi
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004353:Drug Evaluation, Preclinical; D015507:Drugs, Investigational / Q000494:pharmacology*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000235:genetics; D051379:Mice; D009154:Mutation
chemical_list: D015507:Drugs, Investigational