brain cancer Archives - Sanford Burnham Prebys

Tag: brain cancer

Institute News

Sanford Burnham Prebys expert surveys science on how to treat the most common brain cancer

AuthorGreg Calhoun
Date

October 6, 2025

Glioblastoma brain cancer cells under microscope. Image credit: Anna Durinikova/Shutterstock
Glioblastoma brain cancer cells under a microscope. Image credit: Anna Durinikova/Shutterstock.

New editorial recommends a multimodal perspective examining glioblastoma from tumor biology through to surgery

Glioblastoma is one of the most aggressive and treatment-resistant forms of brain cancer. It also is the most common form of cancer that originates in the brain, making research into new and better therapies even more imperative.

Physician–scientist Theophilos Tzaridis, MD, a postdoctoral fellow at Sanford Burnham Prebys Medical Discovery Institute in the lab of Peter Adams, PhD, recently surveyed promising glioblastoma studies after being invited to serve as a guest editor for a special issue of Frontiers in Oncology and Frontiers in Neurology.

More exact and safe surgeries

Tzaridis highlighted two studies focused on improving surgery for glioblastoma, as it continues to be the primary treatment for the disease. The recent publications discussed how to enhance the use of MRI to map out tumors and surrounding tissue, as well as other innovative mapping and monitoring techniques. These approaches would enable neurosurgeons to create better and safer plans for reducing risk of recurrence and avoiding side effects before starting surgery.

Targeted treatments and immunotherapies

Scientists have sought to add treatment options for glioblastoma beyond surgery, radiation therapy and chemotherapy. Some other cancers can be treated with targeted therapies that exploit a unique characteristic of certain tumors, but this approach has yet to yield long-term successes for glioblastoma patients. Tzaridis brought forward a case report of a patient whose tumors were nearly completely cleared by a targeted therapy after chemotherapy was unsuccessful. He suggests that future studies are warranted to identify patient subpopulations that can benefit from these treatments.

Theophilos Tzaridis, MD. Image credit: Sanford Burnham Prebys.

Theophilos Tzaridis, MD, a postdoctoral fellow at Sanford Burnham Prebys Medical Discovery Institute. Image credit: Sanford Burnham Prebys.

Immunotherapies that supercharge the immune system to better detect and eliminate cancer have transformed the treatment of many blood cancers and solid tumors. It has not, however, yet born fruit as an effective treatment for glioblastoma. Tzaridis spotlights a study discussing the potential use of chimeric antigen receptor (CAR) natural killer (NK) cells in glioblastoma rather than the more common CAR T-cell therapies.

The blood brain barrier and brain cancer biology

In addition to demonstrating how research is contributing to improving existing treatments and finding new potential therapies, Tzaridis emphasized the importance of continued studies of brain cancer cell biology and the obstacle to treatment posed by the blood brain barrier. He highlighted two studies focused on overcoming the blood brain barrier along with another two studies regarding cellular models and the use of extracellular vesicles to package and deliver treatments.

“With a multimodal perspective from addressing challenges in neurosurgery to improving our understanding of tumor biology and achieving therapeutic delivery into the brain, we have the best chance of improving survival of patients with this devastating disease,” said Tzaridis.

Institute News

Xueqin Sun awarded $600,000 V Foundation grant to study one of the most common and deadly brain cancers

AuthorGreg Calhoun
Date

September 29, 2025

Xueqin (Sherine) Sun, PhD. Photo credit Sanford Burnham Prebys
Xueqin (Sherine) Sun, PhD. Image credit: Sanford Burnham Prebys

The new award will fund research regarding a hidden weakness in glioblastoma tumors that could lead to a new treatment

Xueqin (Sherine) Sun, PhD, was awarded a three-year, $600,000 V Foundation for Cancer Research grant to study glioblastoma, one of the most common and deadly brain cancers.

Sun will use the award to follow up on her lab’s research regarding a hidden weakness in glioblastoma tumors that could lead to a new treatment. Her team will focus on tumor protein 53, or p53, which normally prevents tumors by detecting DNA damage so it can be repaired, or the cell can self-destruct.

“Think of p53 as the body’s security guard that protects against cancer,” said Sun. In glioblastoma tumors, however, p53 often is unable to do its job.

In nearly three out of every four glioblastoma tumors, another protein called bromodomain-containing protein 8 (BRD8) locks up p53, preventing a key piece of the body’s natural defense mechanisms from fighting back against the growing threat.

“We discovered a way to break apart BRD8, which could free up p53 and let it fight the cancer again,” said Sun.  

The Sun lab will test this approach using lab-grown glioblastoma cells and mini-brain tumor models created from patient samples.

“Our goal is to advance this approach that may lead to new therapeutic strategies for patients facing this devastating disease,” said Sun.

The V Foundation for Cancer Research was founded in 1993 by ESPN and the late Jim Valvano, North Carolina State University basketball coach, ESPN commentator and member of the Naismith Memorial Basketball Hall of Fame. The V Foundation has funded nearly $400 million in cancer research grants in North America.

Institute News

From lab insight to patient impact: Physician–scientist Theophilos Tzaridis on advancing treatments for pediatric brain tumors

AuthorCommunications
Date

September 18, 2025

Theophilos Tzaridis, MD. Photo credit Sanford Burnham Prebys

Recipient of the Fishman Awards: Cynthia Schwartz Shenkman Research Excellence Fishman Award Theo Tzaridis discusses his work on pediatric brain tumors, why rigorous preclinical science matters, and how donor support accelerates discoveries.

Established in 2024, the Cynthia Schwartz Shenkman Research Excellence Fishman Award is unique in nature because it recognizes a Sanford Burnham Prebys postdoc for their outstanding biomedical research contributions and demonstrated track record of research excellence.

What’s your current role and focus at Sanford Burnham Prebys?
I’m a physician–scientist studying pediatric brain tumors. I focus on diffuse midline glioma (DMG). I joined Rob Wechsler-Reya’s group at the institute and benefited from him as an amazing mentor and his expertise in mouse modeling of brain tumors tremendously. After Rob moved institutions, I joined Peter Adams’s lab. Peter’s aging and cancer perspective gives my immunotherapy work a fresh lens and he is a truly spectacular mentor. We’ve built a DMG “niche” in the lab and I’ve deepened my in vivo skills, which are essential for translating ideas toward the clinic.

What drew you into oncology and neurology?
Even in high school I was fascinated by how a cell can go “crazy”, grow uncontrollably and form a tumor. Medicine let me pair that curiosity with real patient impact. My MD thesis work in Heidelberg, Germany, suggested an old chemotherapy could reactivate a tumor suppressor which paved the way for a clinical trial. During my neurology residency in Bonn, Germany, I helped plan, analyze, and published results from  a clinical trial that became the first positive glioblastoma study in 14 years. Those experiences were very rewarding and cemented my focus on translational research.

You mentioned that your approach to immunotherapy starts with “back to basics.” What does that mean?
Many brain tumor trials borrowed targets from other cancers without confirming those targets exist in the brain tumor microenvironment. We went back to basics, systematically profiled immune checkpoint molecules present in DMG and found CD155 (also called the poliovirus receptor) consistently expressed across models and patient samples. That points to smarter targeting rather than one-size-fits-all strategies.

How has the Institute’s environment shaped your work?
The culture at Sanford Burnham Prebys is genuinely team oriented. Core facilities (flow cytometry, mouse) are exceptional partners in experimental design. We also engage in a cross-institution “Brain Tumor Club” on the Mesa and contribute data to a molecular tumor board that informs real treatment decisions. In one case, marker data I generated supported a physician’s plan to pursue a personalized immune therapy known as CAR T-cells for a child which was an incredibly meaningful moment.

Any notable collaborations beyond campus?
Yes. Our in vivo expertise enabled joint studies with Emory University, including work on small molecules for pediatric brain tumors. We have also collaborated with Columbia University and the Dana Farber Institute. These multi-site projects help validate findings independently which is critical in pediatrics where patient numbers are limited.

How did the Fishman Awards affect your trajectory?
The Fishman Career Development Award I received in 2023, and the Cynthia Schwartz Shenkman Research Excellence Fishman Award I recently received provided fuel at key moments. The Fishman Career Development Award sent me to the American Association for Cancer Research (AACR) conference in 2024, where I met a company carrying the only clinical-grade antibody to my target; after an MTA, we’re now testing it here. I also attended the La Jolla Immunology Conference and received a best oral presentation award which is validation that stretching into complex immunology is worth it. Importantly, the Fishman Award application process itself which includes writing, presenting, getting feedback, built resilience and sharpened my vision.

Where do you want to take this next?
I aim to lead an independent lab tightly linked to a clinical trials unit. Success requires basic scientists and clinicians at the same table from day one, plus rigorous preclinical “homework” to identify the subgroups most likely to benefit before launching trials. It’s harder, but in the long run it saves precious time and resources and gives patients better odds.

What is life like outside the lab?
I’m a dad of two, so there is hardly time for anything, but we try to do hikes and some beach time. San Diego’s landscapes are a gift. Before kids I did theater; these days, I read when I can, and we take short family adventures (Anza-Borrego is a favorite).

Is there anything you’d like supporters to know?
Your support is more than funding, it’s belief. At a time when the value of science may be questioned, you’re helping researchers communicate clearly, collaborate widely, and move ideas toward children who can’t wait. The Fishman Awards exemplify that: they strengthen science and the storytelling that brings people along. Thank you.

Institute News

Cancer drug finds new purpose in the brain

AuthorGreg Calhoun
Date

April 14, 2025

MRIs of responding patients throughout the course of avapritinib therapy
These representative MRIs of responding patients show tumors shrinking throughout the course of avapritinib therapy.

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 researchers awarded Curebound grants

AuthorMiles Martin
Date

March 20, 2023

Aninyda Bagchi, PhD, Linda Bradley, Lukas Chavez, PhD, Nicholas Cosford, PhD, and Michael Jackson, PhD

Each year, Sanford Burnham Prebys joins Padres Pedal the Cause, an annual fundraising event that raises money for Curebound which awards collaborative cancer grants in the San Diego area.

These grants include Discovery Grants, which provide seed funds for high-risk/high-reward research in the earliest phases, and Targeted Grants, which are larger awards ($500K) that help translate promising discoveries into treatments for the clinic.

In the 2022-2023 Curebound Research portfolio, five researchers from Sanford Burnham Prebys were awarded grants: Associate Professor Anindya Bagchi, PhD, Professor Linda Bradley, PhD, Assistant Professor Lukas Chavez, PhD, Professor Nicholas Cosford, PhD, and Professor Michael Jackson, PhD

2022 Discovery Grant: Treating incurable pediatric brain tumors 
Bagchi and Chavez will collaborate to advance a new therapeutic approach for medulloblastoma, the most common childhood brain tumor. They will be focusing on a gene called MYC, found only in the deadliest forms of medulloblastoma. This form of brain cancer is currently untreatable, but Bagchi and Chavez recently discovered a molecule that can help control the activity of the MYC gene and potentially inhibit the growth of medulloblastoma tumors. The researcher holds promise to reveal a new treatment approach for this incurable cancer. 

The grant is titled “Decoding the Role of the Long Non-Coding RNA PVT1 in Medulloblastoma.”

2023 Targeted Grant: Discovering a new immunotherapy drug for melanoma
Bradley will be working with Soo Jin Park, MD, from UC San Diego Health to advance a new immunotherapy approach for malignant melanoma. Despite recent advances, this type of skin cancer still causes thousands of deaths in the U.S. each year. The goal of their project is to develop a new drug for melanoma that can reactivate the tumor-killing properties of the patient’s own immune system. This therapeutic approach has the potential to destroy tumors that are resistant to existing therapies, which could help save lives.

The grant is titled, “Advancing Immune Checkpoint Inhibition of PSGL-1 for Treatment of Malignant Melanoma.
 

2022 Discovery Grant: Developing drugs for bone-metastatic prostate cancer
Cosford will work with Christina Jamieson, PhD, from the University of California, San Diego, to advance a new treatment approach for prostate cancer that has spread to the bones. Bone is the most common place for prostate cancer to metastasize, and this form of cancer is currently incurable. The researchers will look for drugs that can kill tumor cells by inhibiting autophagy, a process that promotes tumor progression. The results of the study could identify a new drug ready for clinical trials.

The grant is titled “Pre-Clinical Development of New Autophagy Targeting Drugs for Bone Metastatic Prostate Cancer.”

2022 Discovery Grant: Repurposing drugs for deadly childhood brain cancer
Jackson and Chavez will collaborate to identify new treatment options for ependymoma, an aggressive pediatric brain tumor and leading cause of death among childhood cancer patients. The researchers will screen patient tumor cells against drugs already approved by the FDA for other conditions, looking for drugs that could be repurposed to fight these tumors. Because FDA-approved drugs are known to be safe for humans, this may prove to be the quickest way to help patients currently living with this cancer. 

The grant is titled “High Throughput-Screen for Inhibitors of Pediatric Ependymoma.”

Institute News

Is cloud computing a game changer in cancer research? Three big questions for Lukas Chavez

AuthorMiles Martin
Date

February 22, 2023

Lukas Chavez, PhD

As an assistant professor at Sanford Burnham Prebys and director of the Neuro-Oncology Molecular Tumor Board at Rady Children’s Hospital, Lukas Chavez, PhD, leverages modern technology for precision diagnostics and for uncovering new treatment options for the most aggressive childhood brain cancers.

We spoke to Chavez about his work and asked him how modern technology—particularly cloud computing—is shifting the approach to cancer research.

How are you using new technologies to advance your research?

New technologies are helping us generate a huge amount of data as well as many new types of data. All this new information at our disposal has created a pressing need for tools to make sense of it and maximize their benefits. That’s where computational biology and bioinformatics come into play. The childhood brain cancers I work on are very rare, which has historically made it difficult to study large numbers of cases and identify patterns.

Now, data for thousands of cases can be stored in the cloud. By creating data analysis tools, we can reveal insights that we would never have seen otherwise. For example, we’ve developed tools that can use patient data in the cloud to categorize brain cancers into subtypes we’ve never identified before, and we’re learning that there are many more types of brain tumors than we’ve previously understood. We’re basically transforming the classic histo-pathological approach that people have studied for decades by looking at tumor tissues under the microscope and turning that into data science.

How is cloud computing improving cancer research in general?

Assembling big datasets delays everything, so I believe the main idea of cloud computing is really to store data in the cloud, then bring the computational tools to the data, not the other way around.

My team did one study where we assembled publicly available data, and basically downloaded everything locally. The data assembly process alone took at least two to three years because of all the data access agreements and legal offices that were involved.

And that is the burden that cloud computing infrastructures remove. All of this personalized cancer data can be centrally stored in the cloud, which makes it available to more researchers while keeping it secure to protect patient privacy. Researchers can get access without downloading the data, so they are not responsible for data protection anymore. It’s both faster and more secure to just bring your tools to the data.

Are there any risks we need to be aware of?

Like any new technology, we need to be clear about how we use it. The technology is another tool in the toolbox of patient care. It will never entirely replace physicians and researchers, but it can complement and assist them.

Also, because we use costly and sophisticated tools that are being built and trained on very specific patient groups, we need to be careful that these tools are not only helping wealthier segments of society. Ideally, these tools will be expanded worldwide to help everybody affected by cancer.

Institute News

Brain cancer researcher Jia Zack Shen wins 2022 Eric Dudl scholarship

AuthorMiles Martin
Date

October 18, 2022

Professor Cosimo Comisso, Brett Dudl, Dr. Jim Dudl, Barbra Dudl, and scholarship winner Zack Shen

For the first time since the pandemic, Sanford Burnham Prebys presented the Eric Dudl Endowed Scholarship Award in person at last week’s Cancer Center Open House. This year’s recipient, selected by leaders at the Cancer Center, was Jia Zack Shen, PhD, a staff scientist in the lab of Charles Spruck, PhD The award pays tribute to Eric Dudl, a postdoctoral researcher who succumbed to cancer in 2006, when he was just 33.

“Eric was ill at such a young age, but he was also very lucky because he knew exactly what his dream job was and what his life meant,” says Shen. “Eric’s compassion and dedication to cancer research has been inspiring and encouraging for our postdocs here at Sanford Burnham Prebys. Thank you to the Dudl family for helping me continue my career here.”

Honoring Eric Dudl

In 2005, Eric Dudl had just begun his postdoctoral research in a cancer lab at Sanford Burnham Prebys, where he was known as kind, helpful and a fast learner. Then, at age 32, he was diagnosed with non-small cell lung cancer. This only fueled his fiery passion for cancer research.

“Even when he was very ill, Eric wanted to make a contribution in the time he had,” says Jim Dudl, MD, Eric’s father. “One day I looked at Eric and asked, ‘Why don’t you take some time off work? Get your energy back and go back in when you feel better?’ He looked up at me and said, ‘Why would I do that? This is the best job in the world!’”

Tragically, Eric Dudl would pass away in 2006, at age 33. The next year, his parents established the Eric Dudl Endowed Scholarship Fund to support young cancer researchers like their son.
“These talented scientists pick up where Eric had to leave off,” says Barbara Dudl, Eric’s mother.

Eric Dudl

Eric Dudl

“We are so grateful to the Institute for their compassion for Eric during his illness and helping us create this scholarship. The scientists who are now working on new discoveries might one day save the life of someone like Eric.”

The award presentation was emceed by Cosimo Commisso, PhD, and featured comments from Eric’s parents, as well as his brother, Bret.

“This scholarship fund is the best way we can honor Eric, because he was so passionate about education and supporting others,” says Bret. “The fact that he now helps other postdocs further their work to fight cancer is exactly what he would have wanted.”

Meet the recipient: Jia Zack Shen

Shen started at the Institute as a postdoctoral researcher in 2016, winning a Fishman Fund Award that year. He has since transitioned to a permanent role as a staff scientist, and the funding from this award will help continue to support his role.

“Sanford Burnham Prebys has a great, noncompetitive atmosphere, and the resources we have here are excellent,” says Shen. “Combining cancer research with the drug discovery capabilities we have at SBP is my dream.”

Shen’s research focuses on killing cancer stem cells by shutting off their ability to self-renew and by promoting a response from the immune system, delivering what Shen and his colleagues call a “one-two punch.” Shen has been working specifically on glioblastoma, one of the most aggressive brain cancers.

“Glioblastoma is one of the most devastating diseases, and there is a desperate need for better ways to treat it,” says Shen. “I am working hard to leverage the immune system to fight glioblastoma and save thousands of lives.”

Institute News

Heating up cold brain tumors: An emerging approach to medulloblastoma

AuthorMiles Martin
Date

July 6, 2022

Cancer cells

Immunotherapy has revolutionized cancer treatment, but it doesn’t work on many childhood brain tumors. Researchers from Sanford Burnham Prebys are working to change that.

Brain tumors account for about a quarter of all cancer cases in children. Medulloblastoma, a particularly aggressive form of childhood brain cancer, often develops resistance to radiation and chemotherapy. Researchers from Sanford Burnham Prebys are working to solve this problem by harnessing the power of the immune system.

They describe the potential of this approach in their recently published paper in Genes & Development. 

“The brain’s location makes it very difficult to target medulloblastoma tumors with current therapies,” says first author Tanja Eisemann, PhD, a postdoctoral associate in the lab of Robert Wechsler-Reya, PhD “They’re also immunologically cold, which means they’re good at evading the immune system.” 

The researchers hypothesize that it may be possible to enhance the body’s immune response to medulloblastoma and help the body’s immune cells enter the brain, making treatment with immunotherapy possible.

“Immunotherapy has so much potential as a  cancer treatment, but its scope is limited right now,” says Eisemann. “We want to bring the benefits of this therapy to medulloblastoma patients and their families.”

Eisemann has been studying this approach in mice, and although the research is still at an early stage, she and her colleagues are highly optimistic about its potential.

“The brain has long been considered immune privileged, hidden from immune-system surveillance and immune responses. But we’re starting to see that this isn’t the case,” says Eisemann. “This is a rapidly evolving field, and I’m excited to be working in a lab on the forefront of that research.”

Institute News

Boosting immunotherapy in aggressive brain cancer

AuthorMiles Martin
Date

November 3, 2021

Blue and orange illustration of human brain against black background

Researchers from Sanford Burnham Prebys have collaborated the University of Pittsburgh Cancer Institute to reveal a new approach to enhance the effects of immunotherapy in glioblastoma, one of the most aggressive and treatment-resistant forms of brain cancer.

The study, published recently in Cancer Discovery, describes a novel method to ‘turn off’ cancer stem cells—the malignant cells that self-renew and sustain tumors—enabling the body’s own defense system to take charge and destroy tumors.

“Tumors are more than just masses of cells—each one is a complex system that relies on a vast network of chemical signals, proteins and different cell types to grow,” says senior author Charles Spruck, PhD, an assistant professor at Sanford Burnham Prebys. “This is part of why cancer is so difficult to treat, but it also presents us with opportunities to develop treatment strategies that target the machinery powering tumor cells rather than trying to destroy them outright.”

Glioblastoma is an extremely aggressive form of cancer that affects the brain and the spinal cord. Occurring more often in older adults and forming about half of all malignant brain tumors, glioblastoma causes worsening headaches, seizures and nausea. And unfortunately for the thousands of people who receive this diagnosis each year, glioblastoma is most often fatal.

“We haven’t been able to cure glioblastoma with existing treatment methods because it’s just too aggressive,” says Spruck. “Most therapies are palliative, more about reducing suffering than destroying the cancer. This is something we hope our work will change.”

Immune checkpoint inhibitors—which help prevent cancer cells from hiding from the immune system—can be effective for certain forms of cancer in the brain, but their results in glioblastoma have been disappointing. The researchers sought a way to improve the effects of these medications.

“Modern cancer treatment rarely relies on just one strategy at a time,” says Spruck. “Sometimes you have to mix and match, using treatments to complement one another.”

The researchers used genomic sequencing to investigate glioblastoma stem cells. These cells are the source of the rapid and consistent regeneration of glioblastoma tumors that make them so difficult to treat.

The team successfully identified a protein complex called YY1-CDK9 as essential to the cells’ ability to express genes and produce proteins. By modifying the activity of this protein complex in the lab, the team was able to improve the effectiveness of immune checkpoint inhibitors in these cells. 

“Knocking out this transcription machinery makes it much more difficult for the cells to multiply” says Spruck. “They start to respond to chemical signals from the immune system that they would otherwise evade, giving immunotherapy a chance to take effect.” 

While the approach will need to be tested in clinical settings, the researchers are optimistic that it may provide a way to improve treatment outcomes for people with glioblastoma. 

“What our results tell us is that these cells are targetable by drugs we already have, so for patients, improving their treatment may just be a matter of adding another medication,” adds Spruck. “For a cancer as treatment-resistant as glioblastoma, this is a great step forward.”

Institute News

Conrad Prebys Foundation provides $3 million for pediatric brain cancer research

AuthorSusan Gammon
Date

April 7, 2021

Conrad Prebys Foundation Award

Conrad Prebys was an extraordinary man and a passionate philanthropist. Today, his generosity extends beyond his life through the Conrad Prebys Foundation.

This year, the Foundation provided $3 million to Robert Wechsler-Reya, PhD, and his team of researchers to advance a potential drug to treat medulloblastoma—the most common malignant brain tumor in children.

Children with medulloblastoma often receive aggressive treatment (surgery, radiation and chemotherapy), but many still die of their disease, and survivors suffer long-term effects from therapy. Safer and more effective therapies are desperately needed.

Wechsler-Reya recently combined forces with Michael Jackson, PhD, senior vice president of Drug Discovery and Development, to find a drug(s) that would inhibit the growth of Group 3 medulloblastoma, the most aggressive form of the disease. Using high-throughput screening technology, they identified a compound that reduces levels of a protein called MYC, which is found at exceptionally high levels in Group 3 medulloblastoma, as well as in cancers of the blood, breast, lung and prostate.

“An effective MYC inhibitor could have a major impact on the survival and quality of life of patients with medulloblastoma,” says Wechsler-Reya. “We identified a compound that reduces levels of MYC in medulloblastoma cells, but now we need to learn how it works to optimize it as an anti-cancer drug and advance studies toward the clinic.

“Historically, pharmaceutical companies and funding agencies have under-invested in childhood cancers, and the majority of drugs currently used to treat these cancers were originally developed for adult cancer,” adds Wechsler-Reya. “We believe that effective drugs for pediatric brain tumors must be developed—and this award from the Foundation will help us achieve this goal.”

“We are profoundly grateful to Conrad for his generosity over the years,” says President Kristiina Vuori, MD, PhD “He has a special legacy at our Institute, which was renamed Sanford Burnham Prebys in 2015 to honor him. We are now thankful to his Foundation for including us in their inaugural grant cycle, and for supporting the critical work we do to benefit children and others suffering from cancer.”

The Conrad Prebys Foundation allocated $78 million in its inaugural grant cycle to fund 121 projects. The awards reflect areas of personal interest to Conrad Prebys—including visual and performing arts, higher education, health care, youth development and animal conservation.

Sanford Burnham Prebys joins a long list of recipients, which included other prominent San Diego institutions such as Rady Children’s Hospital, KPBS, San Diego State University, Scripps Research, Museum of Contemporary Art San Diego and the La Jolla Music Society.