By Neuro-Oncology Branch Staff
March 25, 2021
How can we be innovative in our approach to research in order to improve outcomes for central nervous system (CNS) tumors? That is the driving question and force behind the Cancer Metabolism Program at NCI’s Center for Cancer Research, Neuro-Oncology Branch, led by investigator Mioara Larion, Ph.D.
Dr. Larion is a trained biochemist who received a Ph.D. in enzymology from Florida State University. She also holds a M.S. in spectroscopy and B.S. in biochemistry. During her training, she learned about the complexities of enzymes – how they work, the cellular activity, and how mutations cause disease. Eventually, she transitioned towards better understanding diseases and integrating biochemistry with the disease. She sought to find interesting enzymes involved in mutations that cause disease.
Around that time, the isocitrate dehydrogenase (IDH) mutation was discovered in brain tumors. “I started investigating and reading about IDH1, and wanted to understand the enzyme dynamics, biochemistry, and the interaction between function and structure of enzymes,” says Dr. Larion. During her post-doctoral training at Ohio State University, Dr. Larion became interested in metabolism and metabolomics. “That is when I started trying to understand the role of the IDH mutation in the whole metabolism,” says Dr. Larion. This interest led her to neuro-oncology because gliomas commonly have an IDH mutation.
Metabolism and Impact on CNS Tumors
Metabolism is a term used to describe the complex chemical changes that take place in a cell. Metabolomics is the study of substances called metabolites in cells and tissues. Metabolites are small molecules that are made when the body breaks down food, drugs, chemicals, or its own tissue. They can be measured in blood, urine, and other body fluids. Disease and environmental factors, such as diet, drugs, and chemicals, can affect how metabolites are made and used in the body. Metabolomics may help researchers find new ways to diagnose and treat diseases, such as cancer.
Tumor metabolism involves all of the metabolic pathways that are changed due to cancer, including inside the tumor, its surrounding area known as the microenvironment, as well as the alterations in metabolism that occur in the body (systemically) from the tumor. This includes the availability of nutrients that tumor cells can uptake and use. Tumors can use nutrients surrounding the tumor, but they can also restructure metabolic pathways in order to utilize these nutrients. Genetic changes can also allow tumors to thrive in these conditions. These are all key factors that researchers aim to understand when studying tumor metabolism.
IDH mutation is an example of a mutation in a metabolic gene and has a large impact on the prognosis, classification, and treatment of gliomas.
Cancer Metabolism Program
Today, Dr. Larion leads the Cancer Metabolism Program at the Neuro-Oncology Branch and is interested in the metabolic needs of cancer cells and how they process nutrients as a way to potentially delay tumor growth. Her laboratory focuses on studying IDH mutant gliomas, since IDH mutations can cause metabolic changes. Since 2015, she has worked diligently to establish a robust research program to advance the field of cancer metabolism and has expanded her program to include lipid-based research of gliomas.
One recent significant discovery Dr. Larion’s laboratory has found is 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.
Dr. Larion’s motivation stems from the impact her research can have on brain and spine tumor patients in clinic. “My group wants to see that what we find in the lab can be translated into new clinic trials or treatments. We want to find something that can delay the growth of gliomas, in addition to help image the disease and monitor the response to treatments with biomarkers,” says Dr. Larion.
CNS Tumor Metabolism Conference
In an effort to advance the field of CNS tumor metabolism, Dr. Larion and Mark Gilbert, M.D., chief of the National Cancer Institute, Neuro-Oncology Branch, are leading a virtual Joint Symposium: Targeting CNS Tumor Metabolism with the Society for Neuro-Oncology (SNO) on April 6-7, 2021. This will be the first conference that is entirely dedicated to education and research on brain tumor metabolism. The conference registration is free.
The goal of the conference is to “foster collaboration in the area of metabolism, which will positively influence outcomes for patients with CNS cancers,” explains SNO. The conference will bring together clinicians, researchers, trainees, patients, and experts in the field of metabolism. Attendees will walk away with an increased understanding of the benefits of harnessing metabolism in clinical care. “Dr. Gilbert and I recognized the need to bring the neuro-oncology community and the metabolism community together in order to foster future collaborations, as well as to advance the metabolic-based investigation and imaging applications in clinical settings,” explains Dr. Larion.
The focus of the conference is important for researchers and clinicians to understand the metabolic consequences of mutations and how we can use metabolism to delay growth of tumors, improve tumor imaging, and provide information about treatment response or resistance.
Throughout the 2-day symposium, participants will gain new understandings of CNS tumor metabolism using state-of-the-art techniques. There will also be dedicated discussion on interactions between metabolism and epigenomics or transcriptomics. Speakers from across the country will address the current standard of care for patients, as well as the challenges that providers and researchers face in targeting the metabolic signaling pathways. Top experts will share a variety of techniques, including how to prep samples, sequencing best practices, imaging methodologies, and how to analyze data via mass spectrometry.
“The virtual symposium will foster collaboration so we can advance progress in metabolic targets, discuss challenges in the field, learn from each other, and accelerate progress in patient care,” says Dr. Larion.