Acquired platelet antagonism: off-target antiplatelet effects of malignancy treatment with tyrosine kinase inhibitors

B. M. E. Tullemans, J. W. M. Heemskerk, M. J. E. Kuijpers*

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

19 Citations (Web of Science)
37 Downloads (Pure)

Abstract

Platelets can contribute to tumor progression and metastasis. Cancer patients are at increased risk of thrombosis, and advanced stages of cancer are associated with thrombocytosis or increased platelet reactivity. Tyrosine kinase inhibitors (TKIs) are widely used as a targeted strategy for cancer treatment, with the aim of prolonging progression-free survival of the patients. Because of their broad kinase target spectrum, most TKIs inevitably have off-target effects. Platelets rely on tyrosine kinase activity for their activation. Frequently observed side effects are lowering of platelet count and inhibition of platelet functions, whether or not accompanied by an increased bleeding risk. In this review, we aim to give insights into: (i) 38 TKIs that are currently used for the treatment of different types of cancer, either on the market or in clinical trials; (ii) how distinct TKIs can inhibit activation mechanisms in platelets; and (iii) the clinical consequences of the antiplatelet effects of TKI treatment. For several TKIs, the knowledge on affinity for their targets does not align with the published effects on platelets and reported bleeding events. This review should raise awareness of the potential antiplatelet effects of several TKIs, which will be enhanced in the presence of antithrombotic drugs.
Original languageEnglish
Pages (from-to)1686-1699
Number of pages14
JournalJournal of Thrombosis and Haemostasis
Volume16
Issue number9
DOIs
Publication statusPublished - 1 Sep 2018

Keywords

  • cancer
  • platelets
  • signaling
  • therapy
  • tyrosine kinase inhibitor
  • CHRONIC MYELOID-LEUKEMIA
  • CELL LUNG-CANCER
  • CHRONIC LYMPHOCYTIC-LEUKEMIA
  • ENDOTHELIAL GROWTH-FACTOR
  • FACTOR RECEPTOR INHIBITOR
  • BCR-ABL INHIBITOR
  • PHASE-2 TRIAL
  • DOUBLE-BLIND
  • OPEN-LABEL
  • ANGIOGENESIS INHIBITORS

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