Newswise — Like a mystery detective, Sara G.M. Piccirillo, PhD, is hunting deadly bad actors by studying the crime scene and questioning bystanders one by one.
But because the bad actors she’s after are brain cancer cells – and because the bystanders are also cells in the brain – Piccirillo must use scientific methods, not police methods, to stop them in their tracks.
An assistant professor at The University of New Mexico Comprehensive Cancer Center, Piccirillo plans to use two grants, a $250,000 grant from the American Association for Cancer Research (AACR) and Novocure and a $600,000 grant from the Ben and Catherine Ivy Foundation, to study tumor cells and cells in the surrounding area, one by one.
“Glioblastoma is very heterogeneous,” Piccirillo explains. “It is not a single disease. It’s a collection of diseases that ultimately end up looking very similar.”
Even within the same tumor, the cells can differ vastly from each other, and these differences are exactly why she thinks the tumors are prone to recurring and what makes them so difficult to fight.
“They will be very heterogeneous in response to treatment,” she says.
Using the two grants, Piccirillo is focusing on residual disease, the cells that are left behind after surgery and survive treatment with chemotherapy and radiation therapy. Doctors cannot know how these cells will behave; some may seed new, aggressive tumors that resist further treatment.
“What is left behind is not equal to what is taken out,” Piccirillo says, so she is developing new ways to search for and treat these residual cancer cells.
To get a sampling of residual tumor cells, Piccirillo previously adapted a fluorescent technology that helps neurosurgeons to find and remove as much tumor as possible during brain surgery. Given as a drink before surgery, the fluorescent molecule is taken in by tumor cells, allowing the neurosurgeon to distinguish tumor from healthy cells.
In previous studies, Piccirillo’s team learned that in 65% of people with glioblastoma, tumor cells reside in a specific brain structure located outside the surgically removed tumor. Using the AACR grant, she and her team will study how cells in this structure behave before and after treatment with chemotherapy, radiation therapy and a new treatment called electric field therapy.
People with brain cancer who are treated with electric field therapy wear a cap studded with electrodes that create an alternating electric field across the brain, which has been shown in clinical studies to markedly slow brain tumor growth.
Piccirillo will use a device to mimic the electric field on individual cells. And she’s planning to conduct genomic and bioinformatics studies on the cells to learn how their behavior changes. She says, “By using genomic studies, we found that this specific area is responsible for the tumor coming back.”
Piccirillo will use the Ivy Foundation grant to study healthy cells called macrophages in the same area.
Macrophages are immune cells, but they don’t normally live in the brain, which has its own security force of immune cells called microglia. Macrophages can enter the brain and play a key role in inflammation.
“Those macrophages have at least two different identities,” says Piccirillo. “They can try to fight the tumor. Or, unfortunately, they can help the tumor to grow.”
Again, using genomic and bioinformatics analysis, Piccirillo will study macrophages and microglia from the area surrounding the tumor to discover whether they help or hinder its growth. She is excited by the newer technologies available at UNM that allow her to conduct this precise cellular analysis. “We didn’t have the opportunity before to dissect a tumor at the single-cell level,” she says.
Piccirillo hopes that her work in studying the heterogeneity of residual brain cancer cells will help to make advancements in treating glioblastoma.
“And if we can do something on this cancer,” she says, “then most likely there will be information useful for other cancers where these features are not so exacerbated.”
About Sara G.M. Piccirillo, PhD
Sara G.M. Piccirillo, PhD, is an Assistant Professor in the Department of Cell Biology & Physiology, and holds a secondary appointment in the Department of Neurosurgery, at the UNM School of Medicine. She is a full member of the Cellular and Molecular Oncology Research Group at the UNM Comprehensive Cancer Center.
Dr. Piccirillo’s research team includes:
Christian Bowers, MD, Assistant Professor and Vice Chair of Clinical Affairs in the UNM Department of Neurosurgery;
Scott Ness, PhD, Professor in the UNM Department of Internal Medicine Division of Molecular Medicine, Associate Director for Shared Resources and Director of the Analytical and Translational Genomics Shared Resource at the UNM Comprehensive Cancer Center; and
Yan Guo, PhD, Associate Professor in the UNM Department of Internal Medicine Division of Molecular Medicine and Director of the Bioinformatics Shared Resource at the UNM Comprehensive Cancer Center.
About the Grants
The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the AACR, Novocure or the Ivy Foundation.
About The American Association for Cancer Research
Since 1993, the AACR has allocated more than $480 million and awarded over 890 grants to support thousands of scientists devoted to advancing the understanding, prevention, diagnosis, and treatment of cancer. Our grants support researchers domestically and abroad at every stage of their careers, representing a global commitment to cancer prevention, early detection, interception, and cure. Learn more about the 2020-2021 grants and grantees.
The AACR-Novocure Tumor Treating Fields Research Grant represents a joint effort to promote and support independent investigators who are conducting innovative research focused on Tumor Treating Fields. These grants are intended to provide a deeper understanding of the mechanisms of action of this novel anti-cancer treatment modality and to accelerate the development of new treatment strategies to advance therapeutic options for cancer.
About The Ben & Catherine Ivy Foundation
The Ivy Foundation is the nation’s largest privately funded foundation with a mission of improving survival for people diagnosed with a brain tumor. The Ivy Foundation’s approach is to fund patient focused research in gliomas to improve diagnostics and treatments for patients. Since its inception in 2005, the Ivy Foundation has donated over $100 million to cutting-edge research with the expectation that this will lead to an eventual cure for brain cancer. Learn more at ivyfoundation.org. Follow the Ivy Brain Tumor Center on Facebook, Twitter and LinkedIn.
About The University of New Mexico Comprehensive Cancer Center
The University of New Mexico Comprehensive Cancer Center is the Official Cancer Center of New Mexico and the only National Cancer Institute-designated Cancer Center in a 500-mile radius. Its 146 board-certified oncology specialty physicians include cancer surgeons in every specialty (abdominal, thoracic, bone and soft tissue, neurosurgery, genitourinary, gynecology, and head and neck cancers), adult and pediatric hematologists/medical oncologists, gynecologic oncologists, and radiation oncologists. They, along with more than 600 other cancer healthcare professionals (nurses, pharmacists, nutritionists, navigators, psychologists and social workers), provide treatment to 65% of New Mexico’s cancer patients from all across the state and partner with community health systems statewide to provide cancer care closer to home. They treated 13,578 patients in 105,748 ambulatory clinic visits in addition to in-patient hospitalizations at UNM Hospital. A total of 1,610 patients participated in cancer clinical trials, including 696 patients who participated in clinical trials testing new cancer treatments that include tests of novel cancer prevention strategies and cancer genome sequencing. The 102 cancer research scientists affiliated with the UNMCCC were awarded $34.5 million in federal and private grants and contracts for cancer research projects and published 301 high quality publications. Promoting economic development, they filed more than 30 new patents since FY16, and since 2010, have launched 11 new biotechnology start-up companies. Scientists associated with the UNMCCC Cancer Control & Disparities have conducted more than 60 statewide community-based cancer education, prevention, screening, and behavioral intervention studies involving more than 10,000 New Mexicans. Finally, the physicians, scientists and staff have provided education and training experiences to more than 230 high school, undergraduate, graduate, and postdoctoral fellowship students in cancer research and cancer health care delivery. Learn more at cancer.unm.edu.