Second NET SPORE grant at Iowa focused on translating research into improved treatments for patients.

University of Iowa Health Care researchers have been awarded a five-year, $10.7 million Specialized Program of Research Excellence (SPORE) grant from the National Cancer Institute to study new, targeted therapies for neuroendocrine tumors (NETs), which are rare, slow-growing cancers that can arise almost anywhere in the body.

Through this grant, we aim to improve the outcomes of patients with NETs by better understanding the biology of the tumors and developing improved diagnostic and therapeutic approaches - Dawn Quelle, PhD

“These tumors typically don’t respond to traditional cancer treatments,” says Dawn Quelle, PhD, professor of neuroscience and pharmacology in the Carver College of Medicine. She is co-principal investigator of the grant along with James Howe, MD, professor of surgery–surgical oncology and endocrine surgery, and Yusuf Menda, MD, professor of radiology–nuclear medicine. “Through this grant, we aim to improve the outcomes of patients with NETs by better understanding the biology of the tumors and developing improved diagnostic and therapeutic approaches,” Quelle says.

SPOREs are prestigious grants awarded to multidisciplinary teams of scientists who work together to translate cancer research discoveries from the laboratory into clinical practice. The UI is the only institution in the United States to have received a SPORE grant focused on neuroendocrine tumors. The goals and framework of this grant, which brings together over 20 faculty from UI as well as collaborators at Rutgers University, were informed by input from leading NET experts at other institutions and major national NET patient organizations and advocates. Impressively, this is the second NET SPORE grant awarded to UI researchers. The first NET SPORE grant, which ran from 2015 to 2022, built upon clinical and basic science expertise that began to coalesce at Iowa in the early 2000s.

A growing NET problem

While NETs are rare, the number of people diagnosed with these unusual cancers has risen dramatically — approximately 5.2-fold since 1975, according to the research team. By comparison, the average incidence of all other cancers combined is essentially unchanged over that time. Since people with NETs can live with their cancers for decades, this means that the overall number of people living with the disease has also increased greatly.

There are few treatment options for these patients. This is partly because NETs typically grow very slowly and are diagnosed after many years, when they have already spread to other parts of the body. Moreover, most cancer therapies, especially chemotherapies, are designed to attack fast-growing cancer cells and therefore fail to treat sluggish cancers like NETs.

Finding new approaches to untreatable tumors

The NET SPORE provides us a nexus for collaborative basic and clinical science, enabling us to translate our findings into new treatments and give the best, most informed care to these patients - Dawn Quelle, PhD

The NET SPORE at Iowa has four overarching goals:

• Support innovative NET translational research through projects involving laboratory studies and human clinical trials
• Provide administrative, biospecimens, clinical data, and biostatistics support through interactive core research facilities
• Enlist and encourage new translational researchers through developmental and career enhancement programs
• Promote translational NET research through collaborations that result in new treatments and evidence-based guidelines for patients

Three translational research projects will:

• Improve the efficacy of immunotherapy in pancreatic NETs through a new strategy of sensitizing the tumors to immune-enhancing (immune checkpoint inhibitor) therapy, which would deliver a tumor-killing blow while sparing normal tissues
• Develop a new treatment paradigm for patients with lung neuroendocrine cancers by combining drugs that induce metabolic stress with radioligand therapy that targets a novel biomarker specific to these tumors
• Define the potential of commonly used diabetes and obesity drugs (GLP-1 and GIP receptor agonists) to promote unwanted neuroendocrine cancer growth

UI researchers believe this work may guide treatments of other cancers that respond poorly to current therapies, including common malignancies like prostate and breast cancers.

A history of NET research at Iowa

As a result of 25 years of dedication to these patients and this research, NET patients from across North America travel to the Iowa NET clinic, directed by Joseph Dillon, MD, UI professor of internal medicine–endocrinology and metabolism, to receive specialized treatments and access to clinical trials.

UI Health Care has a “high-volume NET clinic because people want to be seen by clinicians who understand this unique disease,” Quelle says. “The NET SPORE provides us a nexus for collaborative basic and clinical science, enabling us to translate our findings into new treatments and give the best, most informed care to these patients.”