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Research Highlight | August 17, 2020

Alberta-based brain researcher team publishes papers in two high-impact journals

Members of a translational research project supported by TFRI from 2012 to 2019 continue to make an impact with two recent publications in important medical research journals. The Alberta-based group, which focuses on improving treatment for patients with aggressive cancers, published new findings based on their early TFRI work in Biomaterials and Neuro-oncology.

The Biomaterials paper, published in May 2020, outlines how the team developed a series of peptides that, when injected into the blood, are able to cross the blood-brain-barrier (BBB) and “home” to glioma cells. This discovery could help deliver drugs and imaging agents into the brain that attach to tumours to improve how doctors see and treat cancers.

“The new technology we’ve created addresses some of the main challenges in brain tumour treatment, which include the difficulty to get things across the BBB and the ability of these treatments to adapt to tumours that are molecularly and phenotypically distinct,” said Dr. Stephen Robbins, a professor at the University of Calgary in the Departments of Oncology and Biochemistry and Molecular Biology, who co-led the team along with Dr. Donna Senger, a research associate professor in the Department of Oncology at UofC. “As a proof of concept, these peptides are being used to improve magnetic resonance imaging (MRI) as well as drug-delivery agents that target therapies directly to glioma cells.”

The team is now working on a partnership with a pharmaceutical company to use these peptides, known as MetaMx, to deliver drugs to the brain to improve outcomes for glioma patients.

Developing a unique model to study glioblastoma

The second study, published in Neuro-oncology (April 2020), presents an in vitro model of the lethal brain cancer glioblastoma (GBM) developed by the group.

According to Dr. Michael Blough, a staff scientist at the Clark Smith Brain Tumour Centre & Charbonneau Cancer Research Institute at University of Calgary, and one of the paper’s lead authors, this model is the first to recapitulate the unique genomic architecture of human GBM.

It is also the first model in which the initiation of GBM can be observed and investigated, enabling the evolutionary trajectory of the cancer to be studied.

“This model 'opens the door' for investigation into the earliest stages of GBM development,” said Dr. Blough. “This has always been a challenge, if not impossible. Our hope is that others will now use our model so we can increase the number of scientists and clinicians exploring the origins of GBM.”

Biomaterials paper

Development of a peptide-based delivery platform for targeting malignant brain tumors

Authors

Jennifer J. Rahn, Xueqing Lun, Selina K. Jorch, Xiaoguang Hao, Chitra Venugopal, Parvez Vora, Bo Young Ahn, Liane Babes, Mana M. Alshehri, J. Gregory Cairncross, Sheila K. Singh, Paul Kubes, Donna L. Senger, and Stephen M. Robbins

Neuro-oncology paper

In vitro modeling of glioblastoma initiation using PDGF-AA and p53-null neural progenitors

Authors

Alexandra K. Bohm, Jessica DePetro,  Carmen E. Binding,  Amanda Gerber, Nicholas Chahley, N. Dan. Berger, Mathaeus Ware, Kaitlin Thomas, U. Senapathi, Shazreh Bukhari, Cindy Chen, Erin Chahley, Cameron Grisdale, Sam Lawn, Yaping Yu, Raymond Wong, Yaoqing Shen, Hiba Omairi, Reza Mirzaei, Nourah Alshatti, Haley Pedersen, Wee Yong, Samuel Weiss, Jennifer Chan, P.J. Cimino, John Kelly, Steve Jones, Eric Holland, Michael Blough, and Gregory Cairncross

Funding

These two studies were partially funded by a Terry Fox Research Institute Translational Research Program Grant to Modeling and Therapeutic Targeting of the Clinical and Genetic Diversity In Glioblastoma Multiforme