By Neuro-Oncology Branch Staff
January 22, 2021
A harmonious team of scientists and health care providers at the Neuro-Oncology Branch (NOB) collaborate to understand the complexities of brain and spine tumors and translate their research to improve treatments. The partnership between our neuro-oncology providers and researchers strengthens the commitment to make significant progress in research and care for patients with central nervous system (CNS) cancers.
With the beginning of the new year, the Neuro-Oncology Branch shares accomplishments made throughout 2020. Together, our clinical team, research laboratories, and staff have made meaningful advances to improve outcomes for patients and their families impacted by brain and spine tumors.
In March, NIH officially went into maximum telework status, and it seemed that we were all thrust into a situation that required us to pivot, adjust, and adapt in a short amount of time. Despite all of this, the NOB was able to adjust and make progress.
The NOB became very well versed with working remotely, particularly in using technology. NOB held regular Branch meetings, educational lectures, journal clubs, and tumor boards virtually. These virtual events allowed NOB staff to be productive and further their research knowledge and skills. The NOB now also uses technology to provide care for patients through telehealth appointments so patients do not need to travel or make unnecessary trips outside their home.
Since the beginning of the pandemic, NOB also had 26 staff, fellows, and special volunteers begin new positions. This includes staff working on developing new therapies, researching patient outcomes, and striving to improve the lives of those with brain and spine tumors. “Although we found creative, new ways to keep advancing care and research at NOB and come together as a team, we all look forward to the time when we can all be together in person once again,” says Mark Gilbert, M.D., chief of the NOB.
Patient Outcomes Program
Led by Terri Armstrong, Ph.D., the Patient Outcomes Program seeks to gain a better understanding of how a patient feels and functions through their disease trajectory and undergoing experimental therapies, how a clinician may better time therapeutic intervention for maximal benefit, and finally, how this will improve long-term care for this subset of patients.
In collaboration with leaders in the field, representatives from regulatory agencies, and patient advocacy representatives, Dr. Armstrong led a working group exploring core constructs to be measured in clinical trials and clinical research which was published in Lancet Oncology this year. “Since the goal of any new treatment is to benefit the patient, it is important to include parameters that measure their clinical outcomes – how the patient feels and functions,” says Dr. Armstrong. The findings in this study support incorporating patient outcomes data into all clinical trials.
Learn more about these findings from Dr. Armstrong and her program in Lancet Oncology.
Translational Research Program
Led by Jing Wu, M.D., Ph.D., the Translational Research Program focuses on developing brain and spine cancer clinical trials that have a strong preclinical rationale. Dr. Wu strives to address gaps in knowledge in neuro-oncology in her laboratory and investigate novel treatment approaches to improve patient clinical outcomes.
In 2020, Dr. Wu’s laboratory investigated the effects of a novel treatment, MRX-2843, in a glioblastoma mouse model. MRX-2843 is a MerTK inhibitor. When MerTK is activated, it causes glioblastoma-associated macrophages and microglia (GAMs) to suppress the immune system and promote tumor growth. “Our findings suggest that MRX-2843 has a therapeutic benefit by causing GAMs to move away from immunosuppressive conditions, preventing neoangiogenesis (formation of new blood vessels) in the glioblastoma microenvironment and inducing tumor cell death,” says Dr. Wu. The findings of this study support developing clinical trials of MRX-2843 in glioblastoma.
Read more about these research findings by Dr. Wu and her laboratory in Neuro-Oncology Advances.
Basic Immunology Program
Masaki Terabe, Ph.D., leads the Basic Immunology Program at the Neuro-Oncology Branch. His research focuses on various aspects of basic immunology, such as examining the biology of Natural Killer T (NKT) cells in brain and spine cancers. NKT cells are a type of immune cell that plays an important role in the body’s immune response and can kill certain cells, such as cancer cells. If NKT cells become inactive, this may contribute to progression of certain diseases, such as cancer.
His research laboratory found that CD1d-restricted NKT cells are involved in the suppression of the immune response against glioblastoma by using a glioblastoma mouse model (SB28 syngeneic orthotopic). “This is the first observation, with our knowledge, strongly indicating that NKT cells are involved in the immune regulation in glioblastoma. By revealing the mechanism used by NKT cells to regulate tumor immunity against glioblastoma, we may be able to discover a new therapeutic target for glioblastoma,” says Dr. Terabe.
Learn more about research advances from Dr. Terabe and his laboratory in Methods in Enzymology.
Translational Immunology Program
Led by Mark Gilbert, M.D., the Translational Immunology Program works to develop combination treatments with immunotherapy that can increase immune cell recruitment to the tumor and improve patient selection in clinical trials to maximize benefit for those enrolled.
Dr. Gilbert’s translational laboratory group worked collaboratively with Javier Gonzalez Alarcon, M.D. to generate an important clinical trial that is designed to determine if they can predict which patients with brain tumors are most likely to respond to immunotherapy. “This involves a blood test performed before treatment with the hope that we will be able to determine which patients should get these treatments,” says Dr. Gilbert. The study will also determine if an immune response in the blood is correlated with a response in the brain tumor.
Read more about research advances from Dr. Gilbert and his laboratory in Neuro-Oncology Advances.
The Cancer Stem Cell Biology Program
Zhengping Zhuang, M.D., Ph.D., leads the Cancer Stem Cell Biology Program. His program uses critical patient observations to drive bench research which may be then translated to clinical use. His laboratory has a longstanding interest and focus on understanding the functional impact of genetic changes that may uncover early disease states and potential treatment opportunities.
In 2020, his lab had an exciting development regarding a promising new drug effective against preclinical glioma models. This drug, TP5, was developed by our collaborator in NINDS a decade ago to inhibit cyclin-dependent kinase 5 hyperactivity in other disease models, including Alzheimer’s and Parkinson’s Disease. Dr. Zhuang’s laboratory is looking to repurpose this agent and found TP5 to be highly effective at treating glioma and colon carcinoma mouse models, and the treatment was well tolerated. “We are excited about the translational potential, and we are working on developing pre-clinical studies on glioblastoma,” says Dr. Zhuang.
Read more about research advances from Dr. Zhuang and his laboratory in Cancers.
Molecular and Cell Biology Program
Led by Chunzhang Yang, Ph.D., the Molecular and Cell Biology Program focuses on the biologic impacts of cancers with isocitrate dehydrogenase (IDH) mutations to uncover selective vulnerability of brain and spine cancers. By understanding the vulnerabilities of brain tumors, this information can be used to generate experimental treatments to improve the current standard of care for patients.
In 2020, his laboratory continued to investigate the mechanism of glioma therapy resistance, looking for a novel therapeutic strategy. “Specifically, we revealed that glutathione metabolism is critical for gliomas with IDH mutation, which was proven to be effective through animal studies,” says Dr. Yang. Glioma with IDH mutation is a recently defined disease cluster where curative therapy remains limited. “Our findings revealed the cancer vulnerability of IDH-mutated glioma, which provides indications for drug discovery and clinical translation,” says Dr. Yang.
Learn more about advancements made in Dr. Yang’s laboratory in Proceedings of the National Academy of Sciences of the United States of America.
Cancer Metabolism Program
The Cancer Metabolism Program, led by Mioara Larion, Ph.D., is interested in the metabolic needs of cancer cells to potentially delay tumor growth. Her laboratory focuses on studying isocitrate dehydrogenase (IDH) mutant gliomas, given the impact that this mutation has on tumor metabolism.
Dr. Larion’s laboratory has found that lipid pathways are important for IDH1-mutant glioma growth and targeting specific enzymes from either fatty acid synthesis or sphingolipid pathway leads to specific cellular death in these cells. “These findings present potential to translate into targets for the development of metabolic therapies that may promote improved outcomes for patients diagnosed with IDH1-mutant gliomas,” says Dr. Larion.
Read more about research advancements from Dr. Larion and her laboratory in Nature Communications.
NCI-CONNECT (Comprehensive Oncology Network Evaluating Rare CNS Tumors) aims to advance education of rare central nervous system (CNS) cancers by building patient-advocacy-provider partnerships and networks to improve care and treatment.
NCI-CONNECT collaborative efforts in research, education and outreach expanded successfully in 2020 through live virtual events. In June, NCI-CONNECT partnered with the National Brain Tumor Society to educate people with brain and spine tumors and their loved ones on how to navigate care through telehealth. In August, it partnered with the Society for Neuro-Oncology (SNO) to educate neuro-oncology providers on patient-centered communications via telehealth. Both events were timely and significant to continue patient care safely and successfully during a global pandemic.
In September, NCI-CONNECT partnered with SNO to host a virtual symposium focused on transdisciplinary global research in rare CNS tumors. The symposium involved world-renowned researchers and health care providers to share their work and address the challenges and possible solutions to improve patient outcomes across CNS cancers. The event demonstrates that global collaborations are essential to advance rare cancer research and education and a starting point to work together to find better answers and outcomes for people with brain and spine tumors.
Read more about progress and advances in clinical care and research with NCI-CONNECT.
The Brain Tumor Trials Collaborative
In an effort to develop and perform state-of-the-art clinical trials, the Neuro-Oncology Branch leads a network of investigators across the nation called the Brain Tumor Trials Collaborative (BTTC). The BTTC strives to advance treatments for primary brain and spine tumors through novel and innovative clinical trial development and recruitment.
In 2020, the NOB restructured their Tumor Board to be held virtually and to integrate BTTC institutions into this highly attended meeting. The integrated tumor boards, which bring together experts in neuro-oncology, neurosurgery, radiation oncology, and neuropathology to review and discuss patient cases, became increasingly important for patients unable to travel at this time. This collaboration allows physicians to work together to provide the best care and treatment plan for patients and families.
The BTTC sites were also invited to join the NCI-CONNECT consortium to perform clinical trials on 12 rare brain and spine tumors. “Using the BTTC multicenter infrastructure to expand rare tumor trials is valuable to this subset of patients who often lack access to treatments specific for their tumor type,” says. Dr. Armstrong.
Read more about progress and advances in clinical trials and collaboration with BTTC.
Continuing Advancements in Research and Clinical Care
Even through the pandemic, we have witnessed some remarkable and highly laudable activities by many in the NOB. “This is exemplified by the teamwork from our clinical group enabling our clinical trials and patient care to continue while maximizing the safety for our patients and staff. Similarly, in the laboratory, the disruption has been met with education and productivity in alternative venues that, combined with an increasing spirit of collegiality, has enabled continued progress,” says. Dr. Gilbert. We are extremely optimistic for what we can accomplish in 2021 and years to come.