![]() The great majority of patients will have to assume TKIs indefinitely – which raises serious pharmacoeconomic concerns and is now shifting the focus from efficacy to compliance and quality of life issues. Only a small proportion of cases may attempt therapy discontinuation without experiencing subsequent relapse. Patients achieving stable optimal responses to TKI therapy are predicted to have the same life expectancy of the general population. ![]() They are more potent molecules, but have been associated to more serious side effects and complications. Second- and third-generation TKIs were later introduced to prevent or counteract the problem of drug resistance, that may arise in a small proportion of patients. ![]() Imatinib mesylate, the first tyrosine kinase inhibitor (TKI) to be approved for therapeutic use, was hailed as a magic bullet against cancer and remains one of the safest and most effective anticancer agents ever developed. BCR-ABL1 was one of the first tyrosine kinases to be implicated in a human malignancy and the first to be successfully targeted. Deregulated activity of BCR-ABL1, a nonreceptor tyrosine kinase encoded by the fusion gene resulting from the t(9 22)(q34 q11) chromosomal translocation, is thought to be the driver event responsible for initiation and maintenance of chronic myeloid leukemia (CML).
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