brain tumors Archives - Sanford Burnham Prebys
Institute News

Cancer drug finds new purpose in the brain

AuthorGreg Calhoun
Date

April 14, 2025

Scientists show that an established cancer drug travels to and shrinks some brain tumors, which may lead to new therapies for a disease with few treatments

Brain tumors are the leading cause of cancer-related death in childhood. The deadliest of these tumors are known as high-grade gliomas, with the grade referring to how quickly certain tumors grow and spread throughout the central nervous system.

Treatment options for high-grade gliomas are limited. Surgical removal is typically the first option depending on the tumor size and location. Radiation often follows to kill any remaining cancer cells to prevent another tumor from forming.

“Drug options to pair with surgery and/or radiation are few and far between,” said Lukas Chavez, PhD, associate professor in the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys. “A big reason for this is the blood-brain barrier being as formidable a boundary as the mythological River Styx.”

The blood-brain barrier can, at times, mean the difference between life and death. It protects the brain and spinal cord from potential toxins and pathogens circulating in the bloodstream. However, in its vigilance, it also blocks beneficial drugs from reaching the brain. This presents a major challenge, since most medications are designed to travel through the bloodstream after being ingested or injected.

Scientists from an international team including Sanford Burnham Prebys, the University of Michigan, Dana Farber Cancer Institute, the Medical University of Vienna and many other institutions published findings March 13, 2025, in Cancer Cell demonstrating that the drug avapritinib could treat certain brain tumor cells. And, like the Styx’s ferryman Charon, the medicine is one of the rare few that can cross the blood-brain barrier known to prevent the passage of more than 98% of small molecule drugs.

The researchers selected avapritinib—which is approved by the Food and Drug Administration for treating gastrointestinal and other cancers—after finding it was the strongest commercially available drug for inhibiting the gene Platelet-derived growth factor receptor alpha (PDGFRA), which is found to be mutated in 15% of high-grade gliomas.

Lukas Chavez, PhD

Lukas Chavez, PhD, is an associate professor in the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys.

In addition to showing that avapritinib inhibited PDGFRA in cancer cells and mouse brain tumors, the research team tested its effects on eight human pediatric and young adult high-grade glioma patients through a compassionate-use program. The treatment was found to be safe and investigators observed that the drug caused tumors to shrink in three patients.

“More research is needed to better understand how to best repurpose this drug for high-grade gliomas,” said Chavez. “We’ll learn a lot from the ongoing Rover study, a phase 1/2 multicenter trial of avapritinib based on these findings that will include more participants.”

The authors of the new study also highlighted the need to study combining multiple targeted therapies to overcome acquired resistance to any single treatment.


Mariella G. Filbin, MD, PhD, assistant professor of Pediatrics at Harvard Medical School and research co-director of the Pediatric Neuro-Oncology Program at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, is the lead contact on the study.

Carl Koschmann, MD, ChadTough Defeat DIPG Research Professor and associate professor of Pediatric Neuro-Oncology at the University of Michigan Medical School, and Johannes Gojo, MD, PhD, head of Pediatric Precision Oncology CNS and ITCC-Lab/Clinical Trials Unit at the Medical University of Vienna, are corresponding authors along with Filbin.

Lisa Mayr, Sina Neyazi, Kallen Schwark and Maria Trissal share first authorship of the study.

Additional authors include:

  • Owen Chapman, Sunita Sridhar, Rishaan Kenkre, Aditi Dutta, Shanqing Wang, and Jessica Wang from Sanford Burnham Prebys
  • Jenna Labelle, Sebastian K. Eder, Joana G. Marques, Carlos A.O. de Biagi-Junior, Costanza Lo Cascio, Olivia Hack, Andrezza Nascimento, Cuong M. Nguyen, Sophia Castellani, Jacob S. Rozowsky, Andrew Groves, Eshini Panditharatna, Gustavo Alencastro Veiga Cruzeiro, Rebecca D. Haase, Kuscha Tabatabai, Alicia Baumgartner, Frank Dubois, Pratiti Bandopadhayay and Keith Ligon from the Dana-Farber/Boston Children’s Cancer and Blood Disorder Center and Harvard Medical School
  • Liesa Weiler-Wichtl, Sibylle Madlener, Katharina Bruckner, Daniel Senfter, Anna Lammerer, Natalia Stepien, Daniela Lotsch-Gojo, Walter Berger, Ulrike Leiss, Verena Rosenmayr, Christian Dorfer, Karin Dieckmann, Andreas Peyrl, Amedeo A. Azizi, Leonhard Mullauer, Christine Haberler and Julia Furtner from the Medical University of Vienna
  • Jack Wadden, Tiffany Adam, Seongbae Kong, Madeline Miclea, Tirth Patel, Chandan Kumar-Sinha, Arul Chinnaiyan and Rajen Mody from the University of Michigan Medical School
  • Alexander Beck from Ludwig Maximilians University Munich
  • Jeffrey Supko and Hiroaki Wakimoto from Massachusetts General Hospital
  • Armin S. Guntner from Johannes Kepler University
  • Hana Palova, Jakub Neradil, Ondrej Slaby, Petra Pokorna and Jaroslav Sterba from Masaryk University
  • Louise M. Clark, Amy Cameron and Quang-De Nguyen from the Dana-Farber Cancer Institute
  • Noah F. Greenwald and Rameen Beroukhim from the Broad Institute of MIT and Harvard
  • Christof Kramm from University Medical Center Gottingen
  • Annika Bronsema from University Medical Center Hamburg-Eppendorf
  • Simon Bailey from Great North Children’s Hospital and Newcastle University
  • Ana Guerreiro Stucklin from University Children’s Hospital Zurich
  • Sabine Mueller from the University of California San Francisco
  • Mary Skrypek from Children’s Minnesota
  • Nina Martinez from Jefferson University
  • Daniel C. Bowers from the University of Texas Southwestern Medical Center
  • David T.W. Jones, Natalie Jager from Hopp Children’s Cancer Center Heidelberg
  • Chris Jones from the Institute of Cancer Research
Institute News

Sanford Burnham Prebys scientists win two American Cancer Society awards

AuthorMonica May
Date

October 1, 2019

Innovation and Collaboration of the Year Awards

The San Diego cancer community—including oncologists, oncology nurses, radiologists, cancer researchers and their friends and family—gathered on September 22 to celebrate progress made in reducing cancer deaths and recognize exceptional individuals and institutions at the inaugural American Cancer Society’s Celebration of Cancer Care Champions in San Diego.

More than 40 finalists were selected, including Sanford Burnham Prebys professors Robert Wechsler-Reya, PhD, who received the Innovation of the Year award for his team’s creation of a new model for studying a brain tumor that commonly arises in infants; and Jorge Moscat, PhD, and Maria Diaz-Meco, PhD, who received the Collaboration of the Year award for their partnership with clinicians at Scripps Clinic who uncovered a novel way to potentially identify a deadly form of colorectal cancer.

Nominations were reviewed by an independent review committee composed of representatives from 10 leading healthcare and research institutions, including Celgene, Kaiser Permanente, Rady Children’s Hospital, Scripps MD Anderson Cancer Center, Moores Cancer Center at UC San Diego Health and more. (Note: Members of the review committee did not score nominations for their own institutions.)

Read on to learn more about our award-winning research:

Innovation of the Year: A new model for studying brain tumors that strike infants
Robert Wechsler-Reya, PhD, a professor at Sanford Burnham Prebys and program director of the Joseph Clayes III Research Center for Neuro-Oncology and Genomics at the Rady Children’s Institute for Genomic Medicine, was honored for his development of a novel mouse model of a pediatric brain tumor called choroid plexus carcinoma. This tumor most commonly arises in infants under the age of one who are too young to undergo radiation treatment. Until now, drug development has been hindered by the lack of models that could help researchers better understand the cancer. Wechsler-Reya and his team have already used the model to identify potential drug compounds that may be therapeutically useful.

Collaboration of the Year (tie): Novel biomarkers to help detect a deadly colorectal cancer 
Sanford Burnham Prebys professors Jorge Moscat, PhD, and Maria Diaz-Meco, PhD; and Scripps Clinic clinicians Darren Sigal, MD, and Fei Baio, MD, were recognized for their successful collaboration. Together, the researchers revealed that loss of two genes drives the formation of the deadly serrated form of colorectal cancer—yielding promising biomarkers that could identify the tumor type. This insight could lead to the development of a diagnostic test to identify serrated colorectal cancer, a hurdle that previously limited our understanding of this deadly cancer type and the development of effective treatments. The research also identified a combination treatment that has treated the cancer in mice.

Institute News

Are stem cells to blame for cancer re-growth?

AuthorBill Stallcup, PhD
Date

July 16, 2017

The scientific and popular media are both full of excitement about the use of stem cell therapies for replacing diseased or damaged tissues. In a new twist to this story, researchers are wondering if small populations of stem cells present in tumors (known as cancer stem cells) may be responsible for the ability of cancers to survive and re-establish themselves, even after the malignancies are apparently eliminated by a combination of surgery, chemotherapy and radiotherapy.

In a new report in the Journal of Clinical Oncology, Robert Wechsler-Reya, PhD, director of the Tumor Initiation and Maintenance Program at SBP, Luis Parada, PhD, from Memorial Sloan Kettering Cancer Center and Peter Dirks, MD, PhD, from Toronto’s Hospital for Sick Children, review the evidence that cancer stem cells may contribute to brain tumor re-appearance. As background, Wechsler-Reya explains that, “There are several good theories about how tumors can develop resistance to therapy and then re-appear after therapy ends. One theory proposes that the unique regenerative properties of cancer stem cells underlies the ability of tumors to rebound.”

So why wouldn’t aggressive cancer therapies destroy cancer stem cells along with the other tumor cells? Significantly, many cancer drugs are designed to be effective against rapidly-proliferating tumor cells. In contrast, both normal stem cells and cancer stem cells often exhibit low rates of proliferation. This allows them to sit quietly on the sidelines, dodging the lethal effects of the therapy and then ramping up their proliferation post-therapy to re-populate the damaged tissue. In the case of normal stem cells this leads to repair of damaged organs, while in the case of cancer stem cells it leads to re-growth of tumors.

According to Wechsler-Reya, some of the best evidence for the existence and power of cancer stem cells comes from studying brain tumors in mice. “Researchers have analyzed several types of mouse brain cancers by separating the tumor cells into pools that carry different markers (like sorting a bag of M&Ms into piles containing the different colors). These separate pools are then injected back into the brains of new mice to compare their tumor-growing abilities. Cells with markers thought to characterize brain tumor stem cells (e.g. the red M&Ms) can produce new tumors even when very few cells are injected. In contrast, the majority of tumor cells (all the other colors of M&Ms) have very poor ability to produce new tumors, highlighting the unique regenerative power of the cancer stem cell population.”

Researchers can now do similar experiments with human brain cancers by injecting tumor cells into special mice that lack an immune system and thus can’t reject the human cells. These studies show that human brain tumors also contain cancer stem cells that can regenerate tumors when transplanted in low numbers. These mouse studies may therefore serve as valuable tools for understanding human brain tumor stem cells and for devising ways to deal with them. For example, researchers hope that cancer stem cells may prove vulnerable to new types of targeted therapies that don’t depend on rapid tumor cell proliferation for their success. Such therapies would destroy cancer stem cells along with the other tumor cells, hopefully avoiding tumor re-growth.

Read a copy of the paper here.

Institute News

Studying “triple threat” protein could lead to new brain cancer treatments

AuthorJessica Moore
Date

April 17, 2017

William Stallcup, PhD, professor at Sanford Burnham Prebys Medical Discovery Institute (SBP), recently published an overview on a protein called NG2 that plays an important role in glioma. Glioma is the most common form of brain cancer, with over 20,000 new cases in the U.S. each year. More than half of all gliomas are classified as glioblastoma, for which the average survival time is only 15 months. We spoke with Stallcup about the implications of NG2 research studies.

What is NG2 and why is it important in glioma?

NG2 is a proteoglycan—a protein on the cell surface with lots of sugars attached to it. It enhances signaling that causes cells to proliferate and move around more easily—exactly what you don’t want in cancer. NG2 is a triple threat because its actions in three cell types help brain tumors grow and spread—the cancer cells themselves, and cells that form new blood vessels that supply tumors with oxygen and nutrients, and immune cells called macrophages, which gliomas convert into their support system. We’ve shown that removing NG2 from any of these cell types slows down glioma growth in mice by 60% or more.

That suggests that blocking NG2 function would be a good way to treat glioma. Is it a good therapeutic target?

To answer that, I should first explain the challenges of treating brain cancer. Not all kinds of drugs can get into the brain, but small molecules can, and those drugs usually block enzymes or receptors. Because NG2 is a different kind of protein, we’d have to think about alternative strategies, like using inhibitory RNAs to reduce production of NG2.

NG2 may also be a good prognostic indicator, since NG2 expression by glioma cells correlates with their malignancy (i.e. the more NG2, the worse the outcome for the patient). Assessing how much NG2 is made by the tumor cells might help guide decisions about how aggressive the treatment strategy should be.

Just as importantly, understanding how NG2 interacts with other proteins to promote glioma growth could point to other ways to stop these tumors from growing. And new drugs are definitely needed—most gliomas are treated with surgery and chemo, which aren’t successful in advanced cases.

What led you to study NG2 and its function in brain cancer?

I actually discovered the protein when I was a postdoc, so my lab has been studying it for the last 30-plus years. A lot of our early work showed how NG2 supports proliferation and migration of immature brain cells during development. When NG2 was found to be present at high levels in glioma, we realized that our expertise put us in a great position to advance knowledge of this often devastating cancer.