Mouse models for pre-clinical drug testing in leukemia. (1st November 2016)

• Record Type: Journal Article
• Authors: Bhatia, Sanil; Daschkey, Svenja; Lang, Franziska; Borkhardt, Arndt; Hauer, Julia
• Is Part Of: Expert opinion on drug discovery. Volume 11:Number 11(2016:Nov.)
• Page Start: 1081
• Page End: 1091
• Publication Date: 2016-11-01
• Subjects: Leukemia -- GEMMs -- gene therapy -- HDACi -- humanized mouse models -- targeted therapy; 615.1
• DOI: 10.1080/17460441.2016.1229297
• Languages: English
• ISSNs: 1746-0441

Abstract

ABSTRACT: Introduction: The development of novel drugs which specifically target leukemic cells, with the overall aim to increase complete remission and to reduce toxicity and morbidity, is the most important prerequisite for modern leukemia treatment. In this regard, the current transition rate of potential novel drugs from bench to bedside is remarkably low. Although many novel drugs show promising data in vitro and in vivo, testing of these medications in clinical phase I trials is often sobering with intolerable toxic side effects leading to failure in FDA approval. Areas covered: In this review, the authors discuss the development of murine model generation in the context of targeted therapy development for the treatment of childhood leukemia, aiming to decrease the attrition rate of progressively complex targeted therapies ranging from small molecules to cell therapy. As more complex therapeutic approaches develop, more complex murine models are needed, to recapitulate closely the human phenotype. Expert opinion: Combining xenograft models for efficacy testing and GEMMs for toxicity testing will be a global approach for pre-clinical testing of complex therapeutics and will contribute to the clinical approval of novel compounds. Finally, this approach is likely to increase clinical approval of novel compounds.