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Investigating PanNET tumorigenesis with single cell genomics

Chang Chan, PhD

Year: 2021
Institution: Rutgers, The State University of New Jersey-RBHS-CINJ
Country: United States
State: NJ
Award Type: Investigator
NET Type: Pancreas
Science Type: Basic

Objective

Matthew Kulke, M.D., will utilize the Neuroendocrine Tumor Bioconsortium 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.

Researchers will evaluate 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. The results will inform our understanding of neuroendocrine tumor prognosis, and biology. The study may also potentially identify new therapeutic targets for NETs.

Research

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.

Publications

Du Y, Ter-Minassian M, Brais L, Brooks N, Waldron A, Chan JA, Lin X, Kraft P, Christiani DC, Kulke MH. Genetic associations with neuroendocrine tumor risk: results from a genome-wide association study. Endocr Relat Cancer. 2016 Aug;23(8):587-94. doi: 10.1530/ERC-16-0171.

Ter-Minassian M1, Chan JA, Hooshmand SM, Brais LK, Daskalova A, Heafield R, Buchanan L, Qian ZR, Fuchs CS, Lin X, Christiani DC, Kulke MH. Clinical presentation, recurrence, and survival in patients with neuroendocrine tumors: results from a prospective institutional database. Endocr Relat Cancer. 2013 Mar 22;20(2):187-96. doi: 10.1530/ERC-12-0340. Print 2013 Apr.