Molecular Analysis of Neuroendocrine Tumor Survival
Researcher: Matthew Kulke, MD Location: Dana-Farber Cancer Institute State: Massachusetts Year: 2011 Status: Finished
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To evaluate whether genetic variation and protein expression in key molecular pathways affect survival in patients with neuroendocrine tumors, and to identify new treatment targets for patients with neuroendocrine tumors.
In this project, Matthew Kulke, M.D., will utilize his extensive Neuroendocrine Tumor Biobank to identify and then confirm predictors of survival in patients with neuroendocrine tumors.
Dr. Kulke will evaluate genetic variation and protein expression in key molecular pathways including the angiogenesis and mTOR signaling pathways. This project will not only inform clinical management of patients but also has the potential to personalize medicine, by identifying markers to select patients for specific targeted therapies, and identify new treatment targets.
To evaluate whether genetic variation and protein expression in key molecular pathways affect survival in patients with neuroendocrine tumors
To identify new treatment targets for patients with neuroendocrine tumors.
The incidence of neuroendocrine tumors is increasing, and the annual prevalence of these malignancies is estimated to exceed 100,000 individuals in the United States. The identification of genetic and molecular prognostic factors for neuroendocrine tumors was identified as a key research priority at a National CancerInstitute summit meeting in September, 2007. Currently used general prognostic factors do not accurately predict the highly variable clinical course of patients with neuroendocrine tumors, some of whom life for decades while others pursue a course that is rapidly fatal.
Our proposed studies leverage the resources of a large database of neuroendocrine tumor patients and specimens, developed by our PI. Our aims are informed by recent preclinical and clinical data suggesting key roles for angiogenesis and mTOR signaling, as well as by a previous analysis of genomic aberrations in neuroendocrine tumors. We propose a two-stage candidate SNP (single nucleotide polymorphism) approach to identify and then confirm genetic predictors of survival in key molecular signaling pathways. The results of our studies will inform our understanding of neuroendocrine tumor prognosis, and biology. Our studies will also potentially identify new therapeutic targets for these diseases.
Research Progress and Results:
Dr. Kulke characterized the mTOR signaling pathway in neuroendocrine tumors, identifying key downstream proteins that are activated and lead to adverse outcomes; these proteins may represent new therapeutic targets. He is currently exploring additional genetic and molecular predictors of both treatment outcome and of neuroendocrine tumor risk that should shed light on new pathways involved in neuroendocrine tumorigenesis, and lead to new therapeutic approaches.
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