NETRF awards six new research grants to improve treatments for neuroendocrine tumors

The Neuroendocrine Tumor Research Foundation (NETRF) today awarded six new research grants totaling $1.85 million to leading academic institutions around the world. The goal of the funding is to improve current treatments for neuroendocrine tumors (NETs), an uncommon and poorly understood cancer, which occurs in the body's hormone-producing cells.

"We are funding projects with the potential to be rapidly transitioned from bench to clinic because time is critical to patients with a rare and advancing cancer," said Elyse Gellerman, NETRF chief executive officer. "NETRF looks to these funded scientists to help solve critical challenges faced by NET patients, families, and clinicians."

"The translational and clinical projects we funded are exciting, ambitious, and diverse, and tackle fundamental problems in NETs, from finding novel and effective ways to block metastases, to creating new radionuclide therapies, and much needed experimental models," said Effie Tzameli, Ph.D., NETRF director of research. "The outcomes of such work will transform our thinking about how NETs spread and develop resistance to treatment, and will help develop new treatments and innovative tools to test new therapies."

The grants fund clinical, translational, and basic research in the United States, Australia, Switzerland, and the United Kingdom. Two of the studies will work towards refining approaches for Peptide Receptor Radionuclide Therapy (PRRT), a treatment modality expanding in the U.S. following the January FDA approval of lutetium Lu 177 dotatate. Other grants focus on developing laboratory models or identifying clinical biomarkers to support drug development. One grant explores a target to inhibit metastasis in pancreatic NETs. All the studies will collectively improve insights for personalized medicine in NETs.

The NETRF grant process is a competitive and structured peer-review process, which starts with an annual global call for letters of intent in late spring. A percentage of those submitting letters are invited to submit full proposals. All responses are reviewed by NETRF's Board of Scientific Advisors and external reviewers. Final approval is made by NETRF's Board of Directors.

"These grants bring us closer to improving the delivery of care with exciting translational and clinical studies that help us work towards improving and expanding patients' treatment options," said George Fisher, M.D., Ph.D., co-chair, NETRF Board of Scientific Advisors.

NETRF funded a record number of 2018 Pilot Projects. "The increased number of Pilot Projects was made possible by the generosity of many people whose lives have been affected by NET cancer, including donors to the year-end appeal, which raised more than $100,000," said Gellerman.

NETRF is the leading private funder of NET cancer research. As a nonprofit 501(c)(3) organization, NETRF is supported by charitable donations from individuals and foundations. A generous gift from The Margie and Robert E. Petersen Foundation funds Accelerator and Petersen Investigator grants as well as other research projects.

Research Grants Approved for Funding by NETRF

2018 Accelerator Grant Award

An integrated preclinical and clinical evaluation of DNA-repair mechanisms in determining response to PRRT as a guide to patient selection and for development of novel combination therapies

Rodney Hicks, M.D., University of Melbourne, Melbourne, Australia

This four-year Accelerator Project will include both laboratory tests and clinical trials aimed at improving the clinical benefits of PRRT. While some patients respond well to PRRT, others are resistant to this type of therapy. By understanding what drives this resistance, investigators hope to improve durable response, and therefore widen the pool of patients who benefit from PRRT. Hicks and colleagues will evaluate the impact of PRRT on tumor cells' ability to recognize and repair radiation damage. To prevent cancer cell repair, the investigators will combine PRRT with therapies that block DNA-repair mechanisms. Laboratory studies will identify which targeted therapies "turn off" cellular repair mechanisms. Then, a pilot clinical trial will test the targeted therapies in combination with PRRT in patients.

2018 Petersen Investigator Grant Award

Simultaneous Auger-e- and β--Particle therapy of metastasized NET using 161Tb-DOTATOC

Roger Schibli, Ph.D., Paul Scherrer Institut, Zurich, Switzerland

This two-year Petersen Project will explore the safety of a novel radionuclide for more effective treatment of NETs. Despite the effectiveness of PRRT to prolong survival, many patients will be diagnosed with metastases a few years later. Schibli and colleagues will develop a new therapy based on terbium radionuclides (161Tb), which have distinct radioactive properties, compared to Lu 177. The researchers will evaluate the ability of 161Tb-DOTATOC to kill single cancer cells and tiny metastases in a pre-clinical setting before they proceed with the first-in-man study. They theorize that this type of therapy will result in a paradigm shift in the treatment of NETs.

2018 Pilot Project Grant Awards

Biomarkers of response to cabozantinib in patients with neuroendocrine tumors

Jennifer Chan, M.D., M.P.H., Dana-Farber Cancer Institute, Boston, MA

This one-year Pilot Project will evaluate data and patient samples from a phase II clinical trial of cabozantinib, a targeted therapy that showed promise in treating NETs. Cabozantinib has been shown to induce cancer cell death in other types of cancers. In this study, Chan and colleagues will analyze samples from their clinical trial to look for biomarkers that could predict response to cabozantinib. Their findings will be applied to a future investigation in a phase III clinical trial of cabozantinib in NET planned by Chan and colleagues.

Exploring the role of epigenetic dysregulation in PanNET progression

Sita Kugel, Ph.D., Fred Hutchinson Cancer Research Center, Seattle, Washington

This one-year Pilot Project will investigate how pancreatic neuroendocrine tumors (PanNETs) spread to other organs in the body. Kugel and colleagues have found that a protein called SIRT6 plays a role in metastasis in PanNETs, in pre-clinical models. The investigators hypothesize that loss of SIRT6 may affect metastatic progression in PanNETs. To test this, they will block SIRT6 to see if tumor cells grow faster in its absence, which would suggest that SIRT6 may block metastasis. Their findings could inform the pursuit of targeted therapies, which could help stop the spread of PanNETs.

Development of Ex-vivo models of metastatic neuroendocrine tumors

Raj Srirajaskanthan, Ph.D., Kings College London, United Kingdom

This one-year Pilot Project aims to develop a laboratory model, whereby neuroendocrine tumors that have spread to the liver will be removed from the patient during surgery and successfully grown in the laboratory. Using precision cut slice technology, the investigators will cut and culture tissue slices from tumor and adjacent healthy tissue in conditions that will maintain their original tissue properties. They will then be able to use this tool to test responses to various drugs. The finding of this study might lead to translational research with the potential to enable the development of personalized medicine for treatment of NETs.

Models of NETs using 3D hydrogels

Charlotte Kuperwasser, Ph.D., Tufts University School of Medicine, Boston, MA

This one-year Pilot Project will aim to develop a new experimental model that can be used to study NET formation and progression. Using 3D hydrogel technology developed in the Piyush Gupta lab at Whitehead Institute--that allows other tumors isolated from patients to grow with greater than 90 percent success--Kuperwasser, Gupta, and colleagues will apply this technique to grow ileum and appendix NETs. The researchers will use this experimental model to understand how NETs grow inside the intestine or the appendix and will try to establish NET cell lines that could ultimately be used to assess therapeutic response.

Source: https://netrf.org/netrf-awards-six-grants/