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Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
10:49

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia

Published on: September 18, 2013

18.8K

How tyrosine kinase inhibitors impair metabolism and endocrine system function: a systematic updated review

Massimo Breccia1, Matteo Molica1, Giuliana Alimena1

  • 1Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy.

Leukemia Research
|December 3, 2014
PubMed

Insights

Tyrosine kinase inhibitors (TKIs) improve chronic myeloid leukemia (CML) outcomes but cause off-target side effects. This review details metabolic changes and mechanisms linked to TKIs like imatinib and newer generations.

Area of Science:

  • Oncology
  • Pharmacology
  • Biochemistry

Background:

  • Tyrosine kinase inhibitors (TKIs) have revolutionized chronic myeloid leukemia (CML) treatment, significantly improving patient response and survival rates.
  • Despite their efficacy, TKIs can cause specific off-target side effects due to the inhibition of various tyrosine kinase receptors (e.g., PDGFR, c-KIT, Src, VEGF).
  • These off-target effects can lead to notable metabolic alterations in patients undergoing TKI therapy.

Purpose of the Study:

  • To comprehensively review the metabolic changes associated with TKI treatment in CML.
  • To explore the potential underlying mechanisms involved in the pathogenesis of these TKI-induced metabolic alterations.
  • To focus on imatinib, second-generation (nilotinib, dasatinib), and third-generation (bosutinib, ponatinib) TKIs.

Main Methods:

  • Literature review of studies investigating TKI side effects and metabolic changes in CML patients.
  • Analysis of preclinical and clinical data on the mechanisms of off-target inhibition by various TKIs.
  • Synthesis of information regarding specific metabolic pathways affected by imatinib, nilotinib, dasatinib, bosutinib, and ponatinib.

Main Results:

  • TKIs targeting BCR-ABL in CML can inhibit other kinases, leading to diverse metabolic consequences.
  • Reported metabolic changes include alterations in lipid metabolism, glucose homeostasis, and potential effects on bone and cardiovascular health.
  • The specific profile of metabolic side effects varies depending on the TKI's selectivity and off-target inhibition profile.

Conclusions:

  • Metabolic changes are a significant class of off-target side effects associated with TKIs used in CML treatment.
  • Understanding these metabolic alterations and their mechanisms is crucial for managing patient health and optimizing TKI therapy.
  • Further research is needed to fully elucidate the long-term metabolic impact and develop targeted management strategies.
Keywords:
EndocrineMetabolicTyrosine kinase inhibitors

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