title: Mouse models for pre-clinical drug testing in leukemia.
abstract: 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.
authors: a Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty , Heinrich-Heine University Dusseldorf , Düsseldorf , Germany.
authors: Sanil
authors: S
authors: Bhatia
authors: a Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty , Heinrich-Heine University Dusseldorf , Düsseldorf , Germany.
authors: Svenja
authors: S
authors: Daschkey
authors: a Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty , Heinrich-Heine University Dusseldorf , Düsseldorf , Germany.
authors: Franziska
authors: F
authors: Lang
authors: a Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty , Heinrich-Heine University Dusseldorf , Düsseldorf , Germany.
authors: Arndt
authors: A
authors: Borkhardt
authors: a Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty , Heinrich-Heine University Dusseldorf , Düsseldorf , Germany.
authors: Julia
authors: J
authors: Hauer
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D002648:Child; D004195:Disease Models, Animal; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D058990:Molecular Targeted Therapy; D013045:Species Specificity; D018675:Toxicity Tests / Q000379:methods; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents
keywords: GEMMs; HDACi; Leukemia; gene therapy; humanized mouse models; targeted therapy