Tyrosine kinases malignancy

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. 

Receptor Tyrosine Kinases and Their Role in Malignancy Targeting the Epidermal Growth Factor Receptor Family Clinical Trials with Anti-HER-2 Strategies Clinical Trials Targeting the EGFR (HER-1)... 

RECEPTOR TYROSINE KINASES AND THEIR ROLE IN MALIGNANCY... 

Rosen L, Hannah A, Rosen P, et al. Phase I dose-escalating trial of oral SU006668, a novel multiple receptor tyrosine kinase inhibitor in patients with selected advanced malignancies. Proc Am Soc Clin Oncol 2000 19 182 (abst). 

Imatinib is an inhibitor of the protein tyrosine kinase involved with platelet-derived growth factor (Bcr-ABL). A loss of cellular control of this tyrosine kinase has been identified as a key mechanism for malignant cell growth. The ability of imatinib to inhibit Bcr-ABL provides a rationale for its use in the treatment of human cancers such as Philadelphia... 

Reardon DA et al (2009) Phase I pharmacokinetic study of the vascular endothelial growth factor receptor tyrosine kinase inhibitor vatalanib (PTK787) plus imatinib and hydroxyurea for malignant glioma. Cancer 115 2188-2198... 

In summary, sunitinib maleate (1) is a multitargeted receptor tyrosine kinase inhibitor with potent anti-angiogenic and antitumor activity. It is approved for the treatment of advanced renal cell carcinoma and gastrointestinal stromal tumors, and is currently undergoing clinical trials for a number of additional malignancies. The discovery synthesis of 1 along with its process development approaches were described in this chapter. 

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