Biomarker to Determine Cancer Patient Response to mTOR Inhibitors
Noninvasive method that utilizes routinely processed patient samples such as serum, peripheral blood mononuclear leukocytes, and tissue samples to identify patients who will respond to mTOR inhibitor therapy.
Identification of decreased VHL levels and the subsequent activation of the HIF pathway in cancer patients can help to predict responders and non-responders of mTOR inhibitor therapy.These biomarkers may be useful for treatment of different cancers since dysregulation of these pathways is also implicated in other cancers including adrenal, brain and ophthalmologic.
UCLA researchers in the laboratories of Drs. George Thomas and Charles Sawyers have found biomarkers that (1) identify kidney cancers that are likely to respond to mTOR inhibitors and (2) measure the efficacy of mTOR inhibitor treatment. Their research shows that decreased expression of the Von Hippel-Lindau tumor suppressor (VHL) is correlated to increased patient sensitivity to the mTOR inhibitor CCI-779, making it a strong biomarker for patients who will respond to treatment with mTOR inhibitors. Additionally, they found that downregulation of the transcription factor subunit HIF1α is a measure of efficacy for mTOR inhibitor treatments. These biomarkers are shown to be measured by several different noninvasive methods.
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Background Inhibitors to the protein kinase mammalian target of rapamycin (mTOR) have been shown to prevent cancer cell growth and proliferation but are only effective in a subset of patients. A reliable, noninvasive biomarker that identifies kidney cancer patients who will likely respond to treatment with mTOR inhibitors could provide clinicians with a tool to better select the appropriate treatment for their patients. Related Materials Tech ID/UC Case 20164/2005-197-0 Related Cases 2005-197-0
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