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Small Molecules in Oncology pp 3–20Cite as

Imatinib Mesylate

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Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 184))

Abstract

IMATINIB MESYLATE (Gleevec, Glivec [Novartis, Basel, Switzerland], formerly referred to as STI571 or CGP57148B) represents the paradigm of a new class of anticancer agents, the so-called small molecules. They have a high selectivity against a specific molecular target known to be the cause for the establishment and maintenance of the malignant phenotype. Imatinib is a rationally designed oral signal transduction inhibitor that specifically targets several protein tyrosine kinases, Abl, Arg (Abl-related gene), the stem-cell factor receptor (c-KIT), platelet-derived growth factor receptor (PDGF-R), and their oncogenic forms, most notably Bcr-Abl. Imatinib has been shown to have remarkable clinical activity in patients with chronic myeloid leukemia (CML) and malignant gastrointestinal stroma tumors (GIST) leading to its approval for treatment of these diseases.

Treatment with imatinib is generally well tolerated with a low incidence of severe side effects. The most common adverse events (AE) include mild to moderate edema, muscle cramps, diarrhea, nausea, skin rashes, and myelosuppression.

Several mechanisms of resistance have been identified. Clonal evolution, amplification, or overexpression of Bcr-Abl as well as mutations in the catalytic domain, P-loop, and other mutations have been demonstrated to play a role in primary and secondary resistance to imatinib, respectively. Improved understanding of the underlying mechanisms of resistance has led to the development of new second-generation tyrosine kinase inhibitors (see Chaps. 7–9).

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  1. Department of Hematology and Oncology, University of Freiburg Medical Center, Hugstetterstraße 55, 79106, Freiburg, Germany

    Cornelius F. Waller

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  1. Medizinische Klinik III, SLK-Kliniken Heilbronn GmbH, Am Gesundbrunen 20-26, Heilbronn, 74078, Germany

    Uwe M. Martens

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Waller, C.F. (2010). Imatinib Mesylate. In: Martens, U. (eds) Small Molecules in Oncology. Recent Results in Cancer Research, vol 184. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-01222-8_1

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