Tyrosine kinase inhibitors are novel therapies targeting specific cellular signalling pathways.
Sunitinib and sorafenib primarily block tyrosine kinase receptors involved in the progression of many tumours, including clear cell renal cell cancer (ccRCC). Although developed to target selected receptors, it is becoming apparent that they inhibit other kinases; this may result in the development of unexpected side effects. This is potentially dangerous as kinases on noncancerous cells are also inhibited. TKI off-target effects contributing to cardiotoxicity, hypothyroidism, hypertension, fatigue, hair depigmentation, hand-foot syndrome and gastrointestinal perforation have been described. We report three patients (3/412) treated with sunitinib and sorafenib who developed chronic myeloid leukaemia (CML) during treatment for ccRCC, proposing a molecular mechanism of tyrosine kinase inhibitors action on bone marrow cells that might be co-responsible for CML development.
Written by:
Czarnecka AM, Oborska S, Rzepecki P, Szczylik C. Are you the author?
Department of Oncology with Laboratory of Molecular Oncology, Military Institute of Medicine, Warsaw, Poland.
Reference: Future Oncol. 2014 Jun 23:1-10.
doi: 10.2217/fon.14.135
PubMed Abstract
PMID: 24953672
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