Dr. Dawn Quelle, PI (UI Pharmacology) along with coIs Mike Knudson (UI Pathology), Joe Galbraith (UI Tissue Procurement Core), Ben Darbro (UI Pediatrics), James Howe (Surgery), Eugene Woltering (LSU, Surgery), and Tanja Milosavljevic (LSU, Surgery), received a NET SPORE Developmental award entitled "Development of Shared Neuroendocrine Tumor PDX Repository".  Neuroendocrine tumors (NETs) are rare, slowly growing neoplasms that arise in many organs, particularly the small bowel and pancreas. They are increasing in incidence and are a significant clinical challenge, in part because NETs are largely resistant to standard anticancer therapies. A better understanding of NET biology, underlying mechanisms of development, and biomarkers for detection and classification is needed to improve patient outcomes. Unfortunately, a significant barrier to NET research is the scarcity of well-validated NET-derived cell lines and model systems for study. Currently, only two pancreatic NET cell lines exist and the single ileal NET line described in the literature is not available to most researchers. There is also an absence of patient-derived xenograft (PDX) models for NETs.

PDX tumors are increasingly being as models of human cancer because they have been shown to most faithfully replicate disease complexity. They are developed from the transplantation of fresh or cryopreserved human tumor samples directly into an immunocompromised mouse. The advantage of this approach is that tumors are never exposed to artificial culture conditions and only passaged in living animals so the PDX models most closely resemble the original human cancer. The National Cancer Institute (NCI) is working intensively to establish PDX models of all human cancers but has not yet been successful for NET PDX. A major disadvantage faced by this NCI initiative is the time delay (~24 hrs) between tumor acquisition and arrival at NCI prior to introduction into immunodeficient mice. Here, we seek to develop the first repository of NET PDX models utilizing high grade cryopreserved NET specimens from LSU Health New Orleans and fresh NET specimens from UI. Both sets of samples are processed shortly after surgical isolation. Therefore, this approach eliminates the greatest challenge to establishing PDX NET tumors, which is time from sample acquisition to introduction into mice or cryopreservation. If successful, this multi-institutional project will develop the first PDXs of ileal and/or pancreatic NETs, which would provide powerful models for investigating NET biology, mechanisms, biomarkers and new anticancer therapies.