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  • Title: [Tyrosine kinase receptor-ras-ERK signal transduction pathway as therapeutic tarfet in cancer].
    Author: Leirdal M, Sioud M.
    Journal: Tidsskr Nor Laegeforen; 2002 Jan 20; 122(2):178-82. PubMed ID: 11873574.
    Abstract:
    BACKGROUND: Experimental evidence indicates that various intracellular signalling cascades are altered in tumour cells. Among these, the receptor tyrosine kinase ras-ERK signalling pathway was found to be constitutively active in a significant percentage of human tumours; hence, considerable effort has been directed at finding compounds that inhibit its activation. MATERIAL AND METHODS: We review the recent progress in establishing novel approaches to interference with the constitutive activation of the receptor tyrosine kinase ras-ERK signalling pathway in cancer. RESULTS: Inhibition of the receptor tyrosine kinase ras-ERK signalling pathway activation by various novel agents (e.g. small molecule tyrosine kinase inhibitors, antibodies, FTase inhibitors, SH2/SH3 directed agents, antisense, ribozymes) impaired tumour growth. Some of the developed agents have been tested in clinical trials; promising results were obtained. INTERPRETATION: Inactivation of the receptor tyrosine kinase ras-ERK signalling pathway by small molecular inhibitors has confirmed its involvement in tumour growth. Thus, molecular and/or pharmacological modulation of the components that are critically involved in the constitutive activation of this pathway are expected to improve the treatment of human malignancies.
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