Research to Improve Survival for Patients with a Deadly Brain Tumor & Role of Sex Differences

    By Kathleen Berger
    Washington University School of Medicine in St. Louis received a $9 million grant from the National Institutes of Health (NIH) to study the life histories of breast and pancreatic cancers. It’s part of the Human Tumor Atlas Network, a large-scale effort to understand the life span of tumors, including how normal cells become cancerous; how the cancer evolves in response to treatment; and what changes must occur for the tumor to become resistant to therapy and spread.

    The project is using advanced technologies to study individual cells. The study involves 3D mapping of tumors and tumor microenvironments for analysis of how the maps change over time.

    “We will understand what’s going on in every single cell,” said principal investigator Li Ding, PhD, an associate professor of medicine at Washington University School of Medicine in St. Louis.

    With 3D mapping, they hope to can gain new insight by studying the disease progression and responses to treatments in up to 300 breast cancer patients and 300 pancreatic cancer patients. But Ding also has plans to launch of a Human Tumor Atlas Network pilot study to map the progression of glioblastoma, a deadly brain tumor.  Researchers say glioblastoma is the most common malignant brain tumor and kills about half of patients within 14 months of diagnosis.

    In order to create the maps, Ding uses detailed genomic analysis to characterize the cells through single cell sequencing. The ability to sequence single cells in a tumor allows researchers to identify which portion of the tumor may survive initial therapy and continue to grow despite aggressive treatments.

    “For this pilot project, we will be using an imaging-guided approach to do the sampling of multiple regions of the brain tumor. Then we are going to analyze each region,” said Ding. “This imaging-guided approach will allow us to precisely map the position of the tumor and allows us to know which part of the brain tumor are most deadly.”

    The process provides the opportunity for scientists to identify immune cells. Single cell sequencing of the cancer microenvironment tells scientists how the patient’s immune system is responding to the tumor invasion.

    Ding explained, “We can bring them back together knowing the genetic alterations in each cell and how they are positioned in relation to each other.”

    Researchers will analyze how the maps change over time. By studying the disease progression, Ding said scientists could help develop better treatment options for future cancer patients with similar cancer cells and similar microenvironments.

    Meantime, researchers at the School of Medicine are already making strides to better understand glioblastoma, which is diagnosed nearly twice as often in males compared with females.

    A team of researchers led by professor of pediatrics and of neuroscience Joshua B. Rubin, MD, PhD, identified distinct molecular signatures of glioblastoma in men and women that help explain why more males get glioblastoma and die from the disease than women.

    The finding suggests that tailoring treatments to men and women with glioblastoma, based on the molecular subtypes of their tumors, may improve survival for all patients.

    Ding said the hope of all efforts by Washington University School of Medicine researchers dedicated to understanding glioblastoma is to develop better treatment options for future cancer patients.  She said the Human Tumor Atlas Network would recommend the most effective treatments for patients with similar cancer cells and similar microenvironments.



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