Yan Receives International Prize for Translational Neuroscience
Duke Cancer Institute brain tumor researcher Hai Yan, MD, PhD, was awarded the International Prize for Translational Neuroscience of the Gertrud Reemtsma Foundation at a ceremony in Cologne, Germany, on August 26, 2021. The prize recognizes Yan’s identification of genetic mutations linked to gliomas, the most common form of primary brain tumors.
Through genomic studies, Yan’s research team found that mutations in the metabolic enzymes IDH1 and IDH2 were present in 70 percent of progressive malignant gliomas. The discovery and subsequent research could provide evidence to support a novel therapeutic approach to the treatment of gliomas.
Yan is the Henry S. Friedman Distinguished Professor of Neuro-Oncology, Professor of Pathology, and member of The Preston Robert Tisch Brain Tumor Center at Duke Cancer Institute.
The International Prize for Translational Neuroscience awards outstanding basic neurological research and includes a prize of 60,000 Euros. The award has been given to scientists from 12 different countries, whose discoveries and contributions represent original and significant achievements. Darell Bigner, MD, PhD, director emeritus of the Preston Robert Tisch Brain Tumor Center, received the award in 2008.
This article originally appeared on the Duke Neurosurgery website and was mirrored here with permission of the author
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A table of posters made by kids and adults for World Cancer Day, Feb. 4, 2022.
Duke Cancer Institute is joining a new initiative with the Global Pediatric Brain Tumor Network, Bayer, the National Brain Tumor Society, other institutions, and Africa partners to "create an equitable ecosystem of care for pediatric brain cancer patients" across the continent of Africa. The announcement was part of a communique issued by The White House on December 14 during the U.S. Africa Leaders Summit.
Using technology from the National Institutes of Health — a common digital platform — the group will connect African hospitals with U.S. hospitals and biomedical innovators in order to improve patient experience and outcomes. Specifically, the initiative will "help match pediatric patients to neuro-oncologists, clinical trials, potential treatments, and organizations that may be able to help close geographic, financial, and cultural barriers."
The new initiative also "aims to contribute to the acceleration of new drug development by participating in multinational pediatric clinical trials and thereby enable earlier access to newer and more innovative therapies for patients in the United States, Africa, and other partner countries."
The pediatric brain cancer initiative is part of a broader White House Cancer Moonshot initiative to dramatically improve cancer outcomes across Africa.
Duke Cancer Institute member H. Kim Lyerly, MD, — the George Barth Geller Distinguished Professor of Immunology, professor of Surgery, professor of Pathology, and executive director of the Center for Applied Therapeutics, Duke University School of Medicine — and pediatric neuro-oncologist Daniel Landi, MD, are co-leaders on the project.
This was one of several new Moonshot-related initiatives announced during the U.S. Africa Leaders Summit.
First launched in 2016 by the Obama administration and led by then-Vice President Joe Biden to “accelerate scientific discovery in cancer, foster greater collaboration, and improve the sharing of cancer data,” the Cancer Moonshot was reignited in February 2022 by President Joe Biden and First Lady Jill Biden, Ed.D. The new goals are to “reduce the cancer death rate by half within 25 years and to improve the lives of people with cancer and cancer survivors.” (The Cancer Moonshot was not active during the Trump administration.)
Duke Health researchers have identified a unique process within the environment of deadly brain tumors that drives resistance to immune-boosting therapies and could be targeted to promote the effects of those drugs.
The finding, published inNature Communications, explains a vexing problem in glioblastoma, a deadly form of brain tumor that has proven notoriously impervious to immune checkpoint inhibitors, a type of immunotherapy, which has been highly effective in other cancers.
“Researchers have traditionally approached immunotherapy and resistance either by looking at cancer cells to find targets to attack or by exploring the tumor environment for potential ways to improve the immune response,” said lead author William H. Tomaszewski, PhD, who conducted the studies as a doctoral candidate in Duke’sDepartment of Neurosurgery. “Our approach in this work was to find environmental factors that could make glioblastoma more vulnerable to immuno-therapies.”
Tomaszewski and colleagues — including senior author John Sampson, MD, professor of neurosurgery — focused on a molecule known as calmodulin-dependent kinase kinase 2, or CaMKK2, which is present in neurons and immune cells. This molecule is highly active in cancer-supporting cells in the glioblastoma environment and is associated with worse survival in humans.
In mouse studies, the cancer-killing T-cells were inhibited from attacking brain tumor cells in animals with high levels of CaMKK2. Among mice bred without CaMKK2, T-cells remained aggressive cancer killers.
Not only did CaMMK2 impact T-cell function, but the protein also changed the behavior of macrophages, making these immune cells less helpful to T-cells. Here again, when CaMMK2 was eliminated, the macrophages aided in tumor killing.
One surprising finding was that CaMKK2, specifically in neurons, was supporting brain tumor growth and suppressing the function of the immune system. Understanding how neurons do this may identify additional therapeutic targets in the future.
Because CaMKK2 is highly expressed in tumor-supporting neurons and macrophages, the researchers said, it promotes resistance to immune-checkpoint inhibitor drugs, which turn off a cellular brake to accelerate the cancer-killing ability of T-cells.
“When mice without CaMMK2 were treated with checkpoint inhibitors, they responded and survived even longer, but mice with CaMKK2 did not,” Tomaszewski said. “This suggests that CaMKK2 represents a potential therapeutic target. If we could inhibit CaMMK2, we might be able to unleash the power of the whole class of immunotherapy drugs that have been beneficial in other cancers, but not glioblastoma.”
In addition to Tomaszewski and Sampson, study authors include Jessica Waibl-Polania, Molly Chakraborty, Jonathan Perera, Jeremy Ratiu, Alexandra Miggelbrink, Donald P. McDonnell, Mustafa Khasraw, David M. Ashley, Peter E. Fecci, Luigi Racioppi, Luis Sanchez-Perez, and Michael D. Gunn.
The study received support from the National Institutes of Health (5R01-NS099463-04, 5U01-NS090284-05, 5P01-CA225622-03, 1R01-CA235612-02, UFDSP00012036, 5P50-CA190991-07, 3P50-CA190991-07S1, 1R01-NS116888-0A1).
