Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Editor

Personal info

View

About

Terms

Javascript disabled

Please enable Javascript support in your browser to use this application.

Instructions on how to enable JavaScript on different browsers can be found here: http://www.google.com/support/bin/answer.py?answer=23852.

[edit this page]

Morimoto, A.M. et al.

Morimoto, Tan, West, McArthur, Toner, Manning, Smolich, Cherrington,

Gene expression profiling of human colon xenograft tumors following treatment with SU11248, a multitargeted tyrosine kinase inhibitor.

Biomarkers that indicate biological activity and/or efficacy are a potentially useful tool in the development of molecularly targeted therapeutics. It is useful, though challenging, to identify biomarkers during preclinical development in order to impact decision-making during early clinical development. SU11248 is an oral, selective multitargeted tyrosine kinase inhibitor currently in Phase II oncology clinical trials. It exhibits direct antitumor and antiangiogenic activity via inhibition of the receptor tyrosine kinases PDGFR, VEGFR, KIT and FLT3. To identify clinically translatable biomarkers of SU11248 activity, expression profiling was performed on Colo205 human xenograft tumors following treatment with SU11248. Over 100 transcripts changed in abundance in SU11248 as compared to vehicle-treated tumors. Nine candidate transcripts, chosen based on putative function, were also analysed and validated by TaqMan. One such potential biomarker, cadherin-11, was further evaluated at the protein level and was found to have increased expression in xenograft tumors after SU11248 treatment. Interestingly, cadherin-11 expression was also detected via immunohistochemical analysis of archived solid tumors, indicating the technical feasibility of translating this putative biomarker to clinical studies. Importantly, SU11248 treatment also resulted in increased expression of cadherin-11 protein in human tumor biopsies in three out of seven patients examined and confirms the feasibility of using transcriptional profiling of preclinical models to identify clinically translatable biomarkers.[1]

References

Gene expression profiling of human colon xenograft tumors following treatment with SU11248, a multitargeted tyrosine kinase inhibitor. Morimoto, A.M., Tan, N., West, K., McArthur, G., Toner, G.C., Manning, W.C., Smolich, B.D., Cherrington, J.M. Oncogene (2004) [Pubmed]

Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenes Open Access Licence Privacy Policy Terms of Use apsburg

The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.