Skeletal Complications of Childhood Cancer

Holm, Ingrid A.

doi:10.1002/9781118453926.ch89

Cited by 1 publication

(1 citation statement)

References 74 publications

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“…Our research described, focused on the question how bone metabolism is affected by TKI treatment as an off-targeted side effect and therewith induced structural and mechanical osseous changes in healthy not-outgrown animals [124]. Bone remodeling has been studied in many species and resulted in the current available knowledge [125][126][127][128][129][130][131]. Evidently, the financial burden of animal maintenance and drug doses to be administered when sequelae of chronic exposure are investigated are much lower using small animals like mice and rats.…”

Section: Other Animal Modelsmentioning

confidence: 99%

Studying Side Effects of Tyrosine Kinase Inhibitors in a Juvenile Rat Model with Focus on Skeletal Remodeling

Tauer¹,

Jäger²,

Ulmer³

et al. 2018

Experimental Animal Models of Human Diseases - An Effective Therapeutic Strategy

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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.

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