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Updated: Mar 15, 2026
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Mouse models for pre-clinical drug testing in leukemia
Sanil Bhatia1, Svenja Daschkey1, Franziska Lang1
1a Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty , Heinrich-Heine University Dusseldorf , Düsseldorf , Germany.
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.
Insights
Developing better preclinical models is crucial for advancing leukemia drug development. Combining xenograft and genetically engineered mouse models (GEMMs) can improve the success rate of novel targeted therapies for childhood leukemia.
Area of Science:
- Oncology
- Pharmacology
- Translational Medicine
Background:
- Modern leukemia treatment requires novel drugs targeting leukemic cells to improve remission and reduce toxicity.
- The transition of potential drugs from laboratory research to clinical application (bench to bedside) is hindered by high failure rates in early clinical trials due to toxicity.
- Existing preclinical models often fail to accurately predict clinical outcomes, leading to drug development attrition.
Purpose of the Study:
- To review the development of murine models for targeted therapy research in childhood leukemia.
- To address the low attrition rate of complex targeted therapies, including small molecules and cell therapies.
- To highlight the need for more sophisticated murine models that closely mimic human disease phenotypes.
Main Methods:
- Discussion of murine model generation for targeted therapy development.
- Analysis of xenograft models for efficacy testing.
- Evaluation of genetically engineered mouse models (GEMMs) for toxicity assessment.
Main Results:
- Complex therapeutic approaches necessitate the development of more complex murine models to accurately recapitulate human phenotypes.
- Combining xenograft and GEMMs offers a comprehensive approach for preclinical testing.
- This integrated strategy is anticipated to enhance the clinical approval rate of novel therapeutic compounds.
Conclusions:
- The development and application of advanced murine models are critical for improving the preclinical evaluation of novel leukemia therapies.
- A combined approach using xenograft and GEMMs for efficacy and toxicity testing, respectively, is proposed.
- This strategy is expected to increase the success rate of novel targeted therapies in clinical trials and contribute to improved patient outcomes.
