Mechanisms and novel approaches in overriding tyrosine kinase inhibitor resistance in chronic myeloid leukemia

Karvela, M., Helgason, G. V. and Holyoake, T. L. (2012) Mechanisms and novel approaches in overriding tyrosine kinase inhibitor resistance in chronic myeloid leukemia. Expert Review of Anticancer Therapy, 12(3), pp. 381-392. (doi: 10.1586/ERA.12.10) (PMID:22369329)

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Chronic myeloid leukemia is a stem cell-initiated but progenitor-driven disease induced by the BCR–ABL oncogene. Tyrosine kinase inhibitors (TKIs) were introduced in the late 1990s and have revolutionized the management of chronic myeloid leukemia in chronic phase. The majority of patients can now expect to live a normal life as long as they continue to comply with TKI treatment. However, in a significant proportion of cases TKI resistance develops over time, requiring a switch of therapy. The most frequent mechanism for drug resistance is the development of kinase domain mutations that reduce or completely ablate drug efficacy. Fortunately, the last 10 years have seen an impressive array of new drugs, some modeled on the mechanism of action of imatinib, others employing more novel approaches, for these patients.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Holyoake, Professor Tessa and Helgason, Professor Vignir and Karvela, Miss Maria
Authors: Karvela, M., Helgason, G. V., and Holyoake, T. L.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Expert Review of Anticancer Therapy
Publisher:Expert Reviews Ltd.
ISSN (Online):1744-8328
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
498551Key survival pathways in chronic myeloid leukaemic (CML) stem cells and novel approaches to their eradicationTessa HolyoakeCancer Research UK (CAN-RES-UK)11008Institute of Cancer Sciences
503111A randomised Phase II trial of Imatinib (IM) versus hydroxychloroquine (HCQ) with IM for patients with chronic myeloid leukaemia (CML) in cytogenic response (CyR)- CHOICESTessa HolyoakeMedical Research Council (MRC)G0900882Institute of Cancer Sciences
439231Is Bcr-Able expression relevant for the survival of cancer stem cells in chronic myeloid leukaemiaTessa HolyoakeMedical Research Council (MRC)G0600782RI CANCER SCIENCES