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Exploring vulnerabilities in cancer stem cells to improve glioblastoma treatments

If you were to look inside a tumour, you’d notice that not all its cells are the same. In fact, over the past decade researchers have found that tumours contain several types of cells, each with specific functions and characteristics.

Cancer stem cells (CSCs) are one of these cell types. Often referred to as the initiating cells of cancer, studies have shown that CSCs often survive therapeutic assault in aggressive cancers, and that when this happens, cancers tend to recur.

The nature of CSCs and the role they play in the recurrence of a deadly brain cancer known as glioblastoma is exactly what Dr. Phedias Diamandis, a neuropathologist at the University Health Network, hopes to explore with his recent Terry Fox New Investigator Award.

“The goal of our study is to understand the biology of CSCs and the role they play in glioblastoma recurrence,” says Dr. Diamandis. “We believe that CSCs evolve to resist traditional therapeutic approaches, and hope that when this happens, they also develop an Achilles heel that we could leverage to target them.” 

As a Terry Fox New Investigator, Dr. Diamandis will receive a total of $450,000 from the Terry Fox Research Institute and the Canadian Institutes of Health Research over the next three years. These funds will help him deploy a novel, three-pronged approach to studying CSCs.

This approach consists of:

  • Using mass spectrometry to see what kind of proteins are active in CSCs and find potential targets for treatment
  • Creating bioengineered brain organoids to model glioblastomas and test novel treatments that targets CSCs
  • Using artificial intelligence to scan histological images of the disease in search for vulnerabilities that stem from the spatial organization of CSCs within the tumour

 “We hope that these activities will help us understand the unique biological aspects of cancer stem cells, their interaction with other cell types in the tumour and, ultimately, their resistance and response to current therapies,” says Dr. Diamandis.

As part of the award, Dr. Diamandis will also receive mentorship from a CIHR-funded research group targeting brain tumour stem cell epigenetic and molecular networks led by Dr. Peter Dirks (SickKids).

“Dr. Diamandis’ project is expected to bring complementary datasets, exciting technologies, and unique expertise to our program,” says Dr. Dirks. “I envision this will great benefit to our research will also provide mentorship that will help Dr. Diamandis continue his outstanding research trajectory.”

The need to study glioblastoma recurrence is clear: it is the most common and aggressive form of brain cancer, affecting approximately four people per 100,000 in Canada. Fewer than five per cent of these patients survive beyond five years, with average survival time being around 15 months. Glioblastoma deaths are ultimately caused by recurrence and resistance to currently available therapies.

“This really is a terrible disease that hasn’t seen meaningful improvement to patient outcomes in 50 to 60 years,” says Dr. Diamandis. “Our hope is that this project can get us one step closer to the development of cancer stem cell-specific therapies that provide a way to debilitate cancer growth in its roots and can provide less toxic and more effective therapies for patients with glioblastoma.”

Read more about all the 2020 Terry Fox New Investigator Award recipients here.

Mentoring Program: SU2C Canada Cancer Stem Cell Dream Team (Targeting Brain Tumour Stem Cell Epigenetic and Molecular Networks) 

Mentor: Dr. Peter Dirks