Tyrosine kinase inhibitor therapy

Hughes TP, et aL Monitoring disease response to tyrosine kinase inhibitor therapy in CML. Hematology Am Soc Hematol Educ Program. 2009 477-87... 

Donato NJ, Talpaz M (2000) Clinical use of tyrosine kinase inhibitors Therapy for chronic myelogenous leukemia and other cancers. Clin Cancer Res 6 2965-2966... 

The t(9 22) has emerged as a sine qua non for the diagnosis of CML, and the recent development of novel tyrosine kinase inhibitor therapy portends a favorable prognosis. By con-... 

Neal JW, Heist RS, Fidias P, Temel JS, Huberman M, Marcoux JP, Muzikansky A, Lynch TJ, Sequist LV. Cetuximab monotherapy in patients with advanced non-small cell lung cancer after prior epidermal growth factor receptor tyrosine kinase inhibitor therapy. J Thorac Oncol 2010 5(11) 1855-8. 

Aribi A, Kantaijian H, Roller C, Thomas D, Faded S, Garda-Manero G, Codes J. The effect of interleukin 11 on thrombocytopenia assodated with tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia. Cancer 2008 113(6) 1338 3. 

Shor, A.C., Agresta, S.V., D Amato, G.Z. Sondak, V.K. Therapeutic potential of directed tyrosine kinase inhibitor therapy m sarcomas. Cancer Control 15, 47-54 (2008). 

BCR-ABL tyrosine kinase that is essential for malignant transformation. Cytogenetic responses to IFN-a therapy were seen in 30-40% of the treated patients with complete responses in about 10%. Long term survival can therefore be expected in these patients. In 2000, the BCR-ABL tyrosine kinase inhibitor Imatinib has been introduced for CML therapy and meanwhile has proven more efficient than IFN-a therapy. 

Sorafenib is a multitargeted cancer therapy that inhibits VEGFR, PDGFR, KIT, fetal liver tyrosine kinase 3 (FLT-3), and the serine/threonine kinase RAF. RAF kinase is a key downstream effector of Ras in the MAPK/Ras signal-transduction pathway that has been linked to various cancers. Sorafenib is both a tyrosine kinase inhibitor and serine/threonine signal-transduction inhibitor. Sorafenib has been approved in renal cancer. 

Targeted Cancer Therapy. Table 2 Main differences between monoclonal antibodies and small-molecule tyrosine kinase inhibitors... 

Note that application in the particular indications is usually restricted either to patients expressing the target (e.g. trastuzumab, cetuximab, lapatinib, imatinib) and/or after failure of prior therapies (e.g. cetuximab, erlotinib, lapatinib, sutinib, dasatinib). Furthermore, for cancer treatment most tyrosine kinase inhibitors are applied in combination with conventional chemotherapeutic drugs, such as fluorouracil, taxanes, platin-based regimens, anthracylines and irinotecan or radiotherapy. 

Gleevec ) is a tyrosine kinase inhibitor used as first-line therapy in the majority of patients with CML. As a potent tyrosine kinase inhibitor, imatinib inhibits phosphorylation of various proteins involved in cell proliferation. Imatinib works by binding to the ATP-binding pocket of BCR-ABL.7 The drug induces complete hematologic responses in more than 95% of patients and complete cytogenetic responses in about 80% of patients in chronic phase.8 Most patients have traces of the disease when measured by RT-PCR and are not cured of their disease. 

Tyrosine kinase inhibitors Antibody Cancer therapy... 

Schlaeppi JM, Wood JM. Targeting vascular endothelial growth factor (VEGF) for anti-tumor therapy, by anti-VEGF neutralizing monoclonal antibodies or by VEGF receptor tyrosine kinase inhibitors. Cancer Metastasis Rev 1999 18 4734-81. 

Adjej, A. (2001). Epidermal growth factor receptor tyrosine kinase inhibitors in cancer therapy. Drugs Future 26(11), 1087-1092. 

Giles F, le Coutre P, Bhalla K et al. A phase II study of nilotinib, a novel tyrosine kinase inhibitor administered to patients with imatinib resistant or intolerant ehronie myelogenous leukemia (CML) in ehronie phase (CP), aeeelerated phase (AP), or blast erisis (BC) who have also failed dasatinib therapy (Abstraet 2170). B/ood2006 108 615a. 

In a small study, imatinib, a tyrosine kinase inhibitor used in the treatment of a number of neoplastic diseases, increased the doses of levothyroxine necessary for adequate replacement therapy (84). 

Shawver, L. K., Slamon, D., Ullrich, A. Smart drugs tyrosine kinase inhibitors in cancer therapy. Cancer Cell 2002, 1, 117-123. 

Bouchet S et al (2010) Therapeutic drug monitoring of tyrosine-kinase inhibitors in the treatment of chronic myelogenous leukaemia interests and limits. Therapie 65 213-218... 

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