NETRF Announces $2.5 Million in Research to Advance the NETs

The Neuroendocrine Tumor Research Foundation (NETRF) continues its aggressive funding of neuroendocrine cancer research with eight new grants totaling $2.5 million. With this newest round of funding, NETRF expands its portfolio to include research into lung neuroendocrine tumors (NETs), which affect about one in four NET patients.

NETRF is the leading private funder of neuroendocrine cancer research, funding more than $26 million in NET research since 2005. NETRF looks for innovative and transformational ideas, such as leveraging findings made in other cancer types to accelerate progress in NETs. The eight new projects explore some of the latest advancements in cancer:

  • CAR T-cell therapy combined with antibody-drug conjugates
  • Photodynamic therapy
  • Deciphering the impact of mutations in key genes in NETs
  • Improving outcomes by combining biomarkers and radiomics
  • “Smart” chemotherapy
  • Novel SSTR2 radioligands
  • Alpha-particle emitting agents for the treatment of lung NETs
  • Testing new cancer vaccines on NETs

As a less common cancer, NETs lag behind other cancers for research funding. “Neuroendocrine tumor is a neglected tumor type that doesn’t get its due funding from federal institutions and other organizations,” said George Fisher, MD, PhD, co-chair, NETRF Board of Scientific Advisors.

NETs occur in hormone-producing cells, most commonly forming in the lung, pancreas, and gastrointestinal tract. Despite appearing in different sites, tumors forming in this cell type are classified as neuroendocrine and require different tests and treatments.

“We are searching out the best science, identifying dedicated investigators, and asking the right questions with the singular goal of trying to identify new treatments, and better ways to manage the disease,” said Dan Chung, MD, co-chair, NETRF Board of Scientific Advisors.

Two U.S. cancer centers will receive their first NETRF grant: Roswell Park Comprehensive Cancer Center, Buffalo, NY, and Moffitt Cancer Center, Tampa, FL.  Two international organizations will also receive their first NETRF grant: BC Canada, Vancouver, Canada, and Radboud University, Nijmegen, Netherlands. Other institutions funded in this grant cycle include the University of Pennsylvania, University of Texas MD Anderson Cancer Center, Stanford University, and the University of California, San Francisco.

“We seek out projects to understand the basic biology of NETs, in addition to research that may be translated from the bench to the clinic to make an impact on patient treatment,” said Elyse Gellerman, NETRF chief executive officer.

The NETRF grant process is a competitive and structured peer-review process, which starts with an annual call for letters-of-intent in late spring. All applications are evaluated by NETRF’s Board of Scientific Advisors. Final approval is made by the NETRF Board of Directors.

As a nonprofit 501(c)(3) organization, NETRF is supported by charitable donations from individuals and foundations. A generous, transformational gift from the Margie and Robert E. Petersen Foundation will fund several of the new projects.  Additional philanthropic support has been provided by from the Goldhirsh-Yellin Foundation of Los Angeles and the Karpus Family Foundation of New York.

Physicians and scientist can sign up to be notified of NETRF grant opportunities.

Accelerator Award

  • Multipronged approaches to develop immunotherapy targeting NETs Xianxin Hua, MD, PhD, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA This 4-year study will develop nanobody-directed CAR T-cell therapy with various combinatory approaches in laboratory models to kill NET cells. The research will be carried out in collaboration with Dr. Carl June at theUniversity of Pennsylvania, whose work was integrally involved with the approval of CAR T-cell therapy, a personalized, breakthrough immunotherapy for blood cancer. The multipronged approaches will significantly increase the opportunity to develop efficacious NET-specific immunotherapy.

Investigator Awards

  • NETcure—shine new light on NET therapy Martin Gotthardt, PhD, Radboud University, Nijmegen, Netherlands An international collaboration in Spain and the Netherlands will explore photodynamic therapy. The team will develop a “photosensitizer,” which is a molecule that upon activation with light induces cell death. The photosensitizer will be coupled with peptides that bind to neuroendocrine tumor cells. The therapy will then be tested and optimized in laboratory models.
  • Understanding the physiologically relevant functions of DAXX Guillermina (Gigi) Lozano, PhD, M.D. The University of Texas Anderson Cancer Center, Houston, TX To build upon an earlier discovery made by NETRF-funded research, investigators will explore the role of DAXX genomic mutations in pancreatic NETs. First, researchers will study the normal functions of the DAXX gene in laboratory models, then evaluate what happens when the gene is removed. This knowledge can help to identify therapeutic targets.
  • New strategies to improve drug development for carcinoid tumors Emily Bergsland, MD, University of California, San Francisco, CA Incorporating serial blood samples and CT scan images from a recently clinical trial, a team of investigators from around the country will explore new approaches to monitoring response: evaluation of multiple proteins in circulating blood, and computational analysis of CT images. This very novel work could lead to the identification of better ways of assessing treatment effects, facilitating testing of the next generation of therapeutic agents in NETs.

Pilot Awards

  • NET-smart chemotherapy: a targeted prodrug strategy Justin Annes, MD, PhD, Stanford University, Stanford, CA By taking advantage of unique properties of NETs that are not found in healthy cells, researchers will try to target chemotherapy to attack only cancer cells, instead of all cells. Creating novel chemotherapeutic agents that will attack and kill only NET cells will help reduce the side effects of currently used systemic chemotherapy.
  • Novel radioligands to improve radiotherapy of NETs Kuo-Shyan Lin, PhD, BC Cancer, Vancouver, Canada Scientists will explore a novel, very stable compound that binds to NET cells’ somatostatin receptors (SSTR2) more tightly than lutetium 177 dotatate (Lu-177). This new radiotherapeutic isotope will be compared with Lu-177 in disease models. Researchers hope “tighter” binding of this radiotherapeutic agent to the cancer cell receptors will lead to higher radiation accumulation and increased cell death.
  • Evaluation of 225Ac-dotatate for treatment of lung carcinoid tumors David Morse, PhD, Moffitt Cancer Center, Tampa, FL Researchers will test a novel radiotherapy, 225Ac-dotatate, a derivative of lutetium 177 dotatate, in PRRT for lung NETs in laboratory models. This therapy emits alpha (α) particles instead of beta (β). Alpha particles are bigger, higher powered, with a shorter reach, which researchers hope will be more effective in killing lung NET cells with decreased toxicity in surrounding normal tissues. Laboratory tests will help evaluate the therapy’s safety and efficacy to prepare for potential testing in humans.
  • Phase 1 study of SurVaxMTM in survivin-positive NETs Renuka Iyer, MD, Roswell Park Comprehensive Cancer Center, Buffalo, NY This study tests the immunotherapy SurVaxM in combination with a somatostatin analog in patients with survivin-expressing NETs. The vaccine targets survivin, a protein that’s often highly expressed in lung, intestinal, and pancreatic NETs and associated with aggressive disease because of its ability to prevent tumor cell death. Many patients with incurable brain cancers on SurvaxM have shown better outcomes than would be expected with standard of care alone.