NETs are rare tumors arising from the diffuse neuroendocrine system, develop in both children and adults, and are dramatically increasing in incidence and prevalence in the US. They are slow growing, difficult to treat malignancies that are resistant to traditional anti-cancer chemotherapies. NET patients often survive longer after diagnosis than people with other cancers, but once tumors become advanced there are few effective treatments. Steve Jobs and Aretha Franklin are two well-known people who had pancreatic NETs. The Quelle lab is part of a large team of investigators at the University of Iowa whose translational studies of NETs are supported by a ‘NET Specialized Program of Research Excellence (SPORE) in Human Cancer’ grant funded by the National Cancer Institute (https://uihc.org/neuroendocrine-spore-overview). Our project aims to identify clinically relevant therapeutic targets that control pancreatic NET (PNET) proliferation and survival. We also seek to establish genetic and proteomic biomarker tests that discriminate NET type and prognosis. These studies, done in collaboration with many clinical and basic science colleagues (particularly Drs. Ben Darbro, Terry Braun, Andrew Bellizzi and James Howe) have uncovered novel pathways driving PNET pathogenesis that may offer new therapeutics options for patients.

Characterizing and Targeting Oncogenic Pathways in Sarcomas

This multi-disciplinary study is aimed at improving treatments for sarcomas, with potential ramifications for many other tumor types. Our group is comprised of experts at the University of Iowa in sarcoma pathways (Dawn Quelle, Benjamin Darbro, Munir Tanas, Rebecca Dodd), tumor genetics (Darbro), veterinary pathology (Meyerholz) and clinical pathology (Tanas, Chuck Lynch), as well as medical oncologists who treat sarcoma / other cancer patients and conduct clinical trials (Varun Monga, Mohammed Milhem). The primary therapeutic targets of this project are regulators within the RABL6A-retinoblastoma (RB1) cancer pathways. The disease of focus is malignant peripheral nerve sheath tumors (MPNSTs), an aggressive and deadly sarcoma of the myelinating nerve sheath that occurs in both children and adults. There are essentially no effective chemotherapies for sarcomas. MPNSTs arise sporadically or by transformation of plexiform neurofibromas (PNFs) in patients with neurofibromatosis type 1 (NF1) disease, and they are the leading cause of death for the over 100,000 people in the US living with NF1. This work addresses an urgent and unmet clinical need for effective, more targeted therapies to treat MPNSTs and other sarcomas