Study to determine if a DNA-based blood test can help detect cancer predisposition in NF1 patients

The Children’s Tumor Foundation (CTF) has announced a groundbreaking 3-year study, which it will fund for nearly $2 million, to determine if a DNA-based blood test can offer better understanding and ultimately earlier diagnosis of cancer predisposition in neurofibromatosis type 1 (NF1) patients. Approximately 7-15% percent of NF1 patients may develop malignant peripheral nerve sheath tumors (MPNSTs), which currently have no cure. Earlier diagnosis could offer patients more options and a better chance at combating these deadly tumors – whether surgically or through other treatment opportunities. Preliminary data has demonstrated that blood test can improve predictability of tumor progression, and major players across the neurofibromatosis (NF) research funding spectrum have agreed that this forthcoming study shows great promise and deserves to be funded.

It is this alignment and collaboration across the NF funding spectrum that is making this research opportunity possible. The Principal Investigators (PIs) of this project are Angela Hirbe, MD, PhD of Washington University and John Shern, MD of the National Cancer Institute (NCI) at the National Institutes of Health (NIH), in PI-level collaboration with Aadel Chaudhuri MD, PhD at Washington University. In their initial proposal to the CDMRP (Congressionally Directed Medical Research Programs), Drs. Hirbe, Shern, and Chaudhuri outlined their plan to offer a relatively simple blood test that offers minimal risk to patients, but may offer the ability to diagnose cancer earlier with the goal of improving outcomes if it allows for more curative surgeries to be performed in the context of smaller and localized tumors, with the goal of leveraging a potential successful study into clinical trials.

Their proposal requested funding as a CDMRP Synergistic Idea Award, aligning with the program’s funding of potential high-impact research opportunities that have historically been neglected. Although the proposal received a very favorable and excellent review, the level of funding needed for the entire study could not be supported thus posing a risk which would result in delays and possibly termination of the study prematurely.

Fortunately, and somewhat uniquely in the medical research ecosystem, major NF funders have been working together so that there is information sharing on projects receiving funding, those that haven’t, what the end goals are, and ensuring that results are shared across the spectrum. Major funders are able to share information regarding research applications submission, funded projects, and pending funding. It is also possible to obtain information such as project aims/goals for projects that did not receive a recommendation to fund. These capabilities ensure transparency across federal agencies and private funders, and it also allows for outcomes and products to be shared across the research spectrum.

In recent years, the effectiveness of this collaborative model resulted in the first ever FDA-approved treatment (selumetinib / Koselugo) for NF patients with inoperable plexiform neurofibromas. (Read more about that ‘MEK Story’ here).

In the instance of this new biomarker study, CTF has committed its support to funding the study in its entirety. The project format is inspired by CTF’s highly effective Synodos model (read more here), which brings top researchers together to solve complex problems in an open and collaborative environment. The researchers commit to the open sharing of data, and an NF patient representative is an essential part of the planning team. In addition to the successful path for selumetinib, CTF’s Synodos model also identified and advanced the testing timeline for brigatinib as a potential treatment for NF2 patients. Brigatinib is currently in clinical trial, in a funding partnership with Takeda.

“We believe that the most effective way to bring treatments to NF patients more quickly is through collaboration and information sharing,” said Annette Bakker, PhD, President of the Children’s Tumor Foundation. “Patients are told to ‘watch and wait’ to see if the tumors grow, which is scary and unfair, so we are highly motivated that the biomarker study proposed by Drs. Hirbe, Shern, and Chaudhuri can potentially flip that scenario when it comes to the deadliest MPNST tumors. We also believe that great science should never stop, and we are proud of our partnership with the CDMRP, the NIH, and other NF funders that projects like this will receive the support they deserve. We have all agreed to communicate openly with each other to benefit our common priority – the health of our NF patients.”

We are thrilled to be able to keep this work moving forward full speed with the support of CTF and the CDMRP. I want to see the day when we can cure all cancers for our patients through early detection.”

Angela Hirbe, MD, PhD

Each year, the NF community advocates on Capitol Hill for NF funding within the CDMRP, which is a program of the Department of Defense. That funding is essential to supporting translational and clinical research projects for NF, including the operation of the NF Clinical Trials Consortium. That support has steadily increased in recent years as representatives from CTF, the CDMRP, the NIH and other NF organizations and funders have shared that this commitment to work together facilitates efficient planning in the use of taxpayer and donor dollars by avoiding duplication and helping scale NF research funding opportunities (essentially, making the dollars spent ‘go farther’). This approach has received an overwhelmingly positive response on the Hill and among donors / funders.

At the center of this important work are the NF patients who will be benefiting from the early detection or even transformation of benign plexiform neurofibromas into MPNST. In order to ensure that patient interests and concerns are infused in the research work from day one, this ‘Synodos for MPNST’ biomarker study will include a patient representative. She/he will bring the patient voice to the table, highlighting both pros and cons of the work proposed, providing input on risk factors, and more.

”Our vision for this project is to push the limits of early detection technologies and our understanding of how NF1 tumors develop,” said Jack Shern, MD. “We believe that the end product of this work is going to be a test that is routinely used in the NF clinic for detection of tumor progression.”

Further details on the study will be announced soon through CTF’s website and social media channels. Patients may also join the NF Registry to receive information on clinical studies taking place for the various forms and manifestations of NF.

NF is a group of genetic disorders that cause tumors to grow on nerves throughout the body. It can cause deafness, blindness, disabling pain, bone abnormalities, learning disabilities, or cancer. CTF is the leading global nonprofit funder of research for all forms of NF. To learn more about the Children’s Tumor Foundation, please visit ctf.org.