**Author details**

Ljubica Gavrilović\*, Vesna Stojiljković, Nataša Popović, Snežana Pejić, Ana Todorović, Ivan Pavlović and Snežana B. Pajović

\*Address all correspondence to: gljubica@vinca.rs

Institute of Nuclear Sciences "Vinča", Laboratory of Molecular Biology and Endocrinology, University of Belgrade, Belgrade, Serbia

[11] Gavrilović L, Spasojevic N, Dronjak S. Chronic individual housing-induced stress decreased expression of catecholamine biosynthetic enzyme genes and proteins in

Animal Models for Chronic Stress-Induced Oxidative Stress in the Spleen: The Role of Exercise...

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305

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**Chapter 15**

**Provisional chapter**

**Studying Side Effects of Tyrosine Kinase Inhibitors in a**

**Juvenile Rat Model with Focus on Skeletal Remodeling**

**Studying Side Effects of Tyrosine Kinase Inhibitors in a** 

DOI: 10.5772/intechopen.70006

**Juvenile Rat Model with Focus on Skeletal Remodeling**

The tyrosine kinase (TK) inhibitor (TKI) imatinib provides a highly effective treatment for chronic myeloid leukemia (CML) targeting at the causative oncogenic TK BCR-ABL1. However, imatinib exerts off-target effects by inhibiting other TKs that are involved, e.g., in bone metabolism. Clinically, CML patients on imatinib exhibit altered bone metabolism as a side effect, which translates into linear growth failure in pediatric patients. As TKI treatment might be necessary for the whole life, long-term side effects exerted on bone and other developing organs in children are of major concern and not yet studied systematically. Here, we describe a new juvenile rat model to face this challenge. The established model mimics perfectly long-term side effects of TKI exposure on the growing bone in a developmental stage-dependent fashion. Thus, longitudinal growth impairment observed clinically in children could be unequivocally modeled and confirmed. In a "bench-to-bedside" manner, we also demonstrate that this juvenile animal model predicts side effects of newer treatment strategies by second generation TKIs or modified treatment schedules (continuous vs. intermittent treatment) to minimize side effects. We conclude that the results generated by this juvenile animal model can be directly used in

the clinic to optimize treatment algorithms in pediatric patients.

**Keywords:** juvenile, growth, bone, tyrosine kinase inhibitor, side effects, CML

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

and reproduction in any medium, provided the original work is properly cited.

The introduction of tyrosine kinase inhibitors (TKIs) for targeted treatment of chronic myeloid leukemia (CML) marked a paradigm shift in the field of hemato-oncology [1, 2]. However, soon after CML became most successfully treated cancer—first in adults and thereafter in

Josephine T. Tauer, Bernadette A. S. Jäger, Anna Ulmer, Paula Geidel, Vera Girke, Lysann Kroschwald and Meinolf Suttorp

Josephine T. Tauer, Bernadette A. S. Jäger, Anna Ulmer, Paula Geidel, Vera Girke, Lysann

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.70006

**Abstract**

**1. Introduction**

Kroschwald, and Meinolf Suttorp


**Provisional chapter**
