Tyrosine Kinase Inhibitors: A Review on Pharmacology, Metabolism, and Side Effects
June 2009
in “
Current drug metabolism
”
tyrosine kinase inhibitors TKIs imatinib gefitinib erlotinib sorafenib sunitinib dasatinib folliculitis paronychia facial hair growth erythema frontal alopecia VEGFR PDGFR FLT3 periorbital edema hypothyroidism Gleevec Iressa Tarceva Nexavar Sutent Sprycel hair follicle inflammation nail infection redness hair loss vascular endothelial growth factor receptor platelet-derived growth factor receptor FMS-like tyrosine kinase 3 swelling around the eyes underactive thyroid
TLDR Tyrosine kinase inhibitors effectively treat cancers but often cause skin and other side effects.
Tyrosine kinase inhibitors (TKIs) were effective in treating various malignancies by competitively inhibiting ATP at the tyrosine kinase catalytic binding site. Imatinib was the first TKI introduced, followed by gefitinib, erlotinib, sorafenib, sunitinib, and dasatinib. Despite their shared mechanism, TKIs differed in targeted kinases, pharmacokinetics, and adverse effects. Skin toxicity, including folliculitis, occurred in over 50% of patients, with erlotinib and gefitinib causing the most skin and hair issues, such as folliculitis, paronychia, facial hair growth, erythema, and frontal alopecia. Sorafenib and sunitinib, targeting VEGFR, PDGFR, and FLT3, rarely caused folliculitis but were linked to subungual splinter hemorrhages. Imatinib commonly caused periorbital edema. Common side effects included edema, nausea, hypothyroidism, vomiting, and diarrhea, with potential long-term cardiac toxicity debated for imatinib and sunitinib. Despite these effects, TKIs were generally well tolerated.
