The incidence of Neuroendocrine Tumors (NETs) has increased five-fold over the last three decades, and many patients do not develop symptoms until the tumors have metastasized. Although patients with these tumors may have prolonged survival despite advanced stage, further understanding of the molecular biologic basis of NETs holds the promise for improved diagnosis, imaging, and therapy. We hypothesize that analyzing the gene expression profiles of these tumors and their exomes will allow us to identify important genes that will facilitate clinical advances for patients with these tumors. This contribution will be significant because it will allow us to determine the tumor site of origin in patients presenting with liver metastases and unknown primaries, which will lead to more directed surgical exploration and resection; and knowledge of cell surface receptors or other genes significantly over-expressed in NETs relative to normal tissues will facilitate the development of new targets for detection, imaging, and medical management. Novel targets for therapy will also be suggested by the identification of frequently mutated or deleted genes in these tumors or the germline of patients with familial NETs.
Understanding the gene expression and mutational profiles of NETs represents an ideal opportunity for developing new diagnostic, imaging, and therapeutic modalities for these tumors. The proposed studies will result in several promising new therapeutic strategies in patients with NETs: 1) determining gene expression profiles to distinguish the site of origin of unknown primaries; 2) identifying new targets for ligands to be utilized in Project 1; and 3) uncovering additional genes and pathways important in the progression of primary tumors and their metastases.
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