6533b82dfe1ef96bd129158b
RESEARCH PRODUCT
Tyrosine Kinase Inhibitors for the Treatment of Chronic Myeloid Leukemia
Francesco DieliManlio TolomeoDaniele SimoniNicola Gebbiasubject
Cancer ResearchFusion Proteins bcr-ablAntineoplastic AgentsApoptosisPharmacologyhemic and lymphatic diseasesLeukemia Myelogenous Chronic BCR-ABL PositivemedicineHumansProtein kinase AneoplasmsProtein Kinase InhibitorsPharmacologyTyrosine kinase inhibitorsABLbusiness.industryBcr-Abl chronic myelogenous leukemia tyrosine kinase inhibitorsMyeloid leukemiaImatinibProtein-Tyrosine Kinasesmedicine.diseaseBcr-Abl; Chronic myelogenous leukemia; Tyrosine kinase inhibitors;LeukemiaImatinib mesylateCancer researchMolecular MedicinebusinessTyrosine kinaseChronic myelogenous leukemiamedicine.drugChronic myelogenous leukemiaBcr-Abldescription
Imatinib mesylate (Gleevec) is a drug unique for the treatment of certain forms of cancer. It works by targeting, and turning off, specific tyrosine kinase proteins that cause the uncontrolled cell growth and the inhibition of apoptosis in cancer cells. Imatinib was designed on the basis of the structure of the ATP binding site of the Abl protein kinase with the aim to stabilizes the inactive form of Bcr-Abl, an oncoprotein involved in malignant transformation in chronic myelogenous leukemia (CML). However, imatinib can also target other tyrosine kinase proteins different from Bcr-Abl such as Kit, that is the suspected cause of gastrointestinal stromal tumor (GIST). Despite successful clinical results observed in the last years, the long-term effects of imatinib and its ability to completely eradicate CML are still unknown. Moreover, similar to many other anti-cancer drugs, clinical resistance to imatinib has emerged. In this review we will discuss the in vitro and in vivo results obtained with the novel tyrosine kinase inhibitors developed to overcome imatinib resistance in Bcr-Abl expressing hematologiocal disorders.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2009-01-01 |