title: Adverse cutaneous reactions secondary to tyrosine kinase inhibitors including imatinib mesylate, nilotinib, and dasatinib.
abstract: Imatinib mesylate is the first of a novel group of drugs that specifically target protein tyrosine kinases, which are central to the pathogenesis of human cancer. It has been approved for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumor and has been found efficacious in other neoplastic diseases. Nilotinib and dasatinib, a second-generation of tyrosine kinase inhibitors (TKIs), were developed in response to findings of emerging imatinib resistance or intolerance to the drug. Cutaneous reactions are the most common nonhematologic side effect of these drugs, and their management is challenging especially in the absence of alternative anticancer agents. The present review focuses on the clinical characteristics and the hypothesized molecular pathogenesis of these first- and second-generation TKIs' cutaneous side effects, and approaches to their treatment. The wide range of adverse effects clarifies the difficulty in designing a truly antitumoral TKI.
authors.affiliation: Department of Dermatology, Davidoff Center, Rabin Medical Center, Beilinson Hospital, Tel Aviv University, Israel. amitay2@zahav.net.il
authors.forename: Iris
authors.initials: I
authors.lastname: Amitay-Laish
authors.forename: Salomon M
authors.initials: SM
authors.lastname: Stemmer
authors.forename: Mario E
authors.initials: ME
authors.lastname: Lacouture
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001549:Benzamides; D000069439:Dasatinib; D003875:Drug Eruptions / Q000209:etiology* / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; C498826:nilotinib; D000069439:Dasatinib