Do Bad Stem Cells Cause Tumours?

Brain tumours are resistant to the best cancer therapies available. One theory about their cause could help lift patients' chances of survival.

 |  Transcript [PDF]

Why do some cancers go away and others come back time and time again? Pediatric neurosurgeon Sheila Singh believes the answer lies in cancer stem cells.

Brain tumours are one of the most aggressive types of tumours and despite gold standard therapy – surgery, radiation, chemotherapy – patients usually have only months to live after diagnosis with cancers like glioblastoma. Despite the current odds, Singh, a stem cell scientist at McMaster University, knows we can do better.

In Singh’s experience, two patients could have the exact same cancer and same clinical care but very different outcomes. She went into research because she knew she would never be able to explain why one patient would live while the other died if she just studied clinical neurosurgery – the answer was in molecular biology.

During the pediatric neuropathology rotation of her neurosurgery residence, Singh saw that tumours that appeared the same on the surface were actually heterogeneous, meaning they were made up of different cell types.

“It’s a challenge and an inspiration to take care of children when they are sick,” says Singh. “Children don’t feel sorry for themselves when something bad happens to them. They just keep on moving.”

Today, Dr. Singh and her research group are trying to parse out those different cell types and determine their properties, functions, and how they arise in the body. Singh believes that there must be some cells types within a tumour that are escaping all of the gold standard therapies and lying dormant only to arise again after the treatment is completed causing the patient to relapse and die.

She thinks that those cells are abnormal stem cells. In understanding how stem cells develop, how they evade therapy and how they cause tumours to recur, Singh’s group at the McMaster Stem Cell and Cancer Research Institute hopes they will be able to determine how to better target these cells and eradicate the tumour completely, so that the patient can survive.

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Dr. Sheila Singh is an associate professor of surgery and biochemistry, a pediatric neurosurgeon at McMaster Children’s Hospital, and scientist appointed to the Stem Cell and Cancer Research Institute at McMaster University.  She holds a Tier 2 Canada Research Chair in Human Cancer Stem Cell Biology, and is Director of the McMaster Surgeon Scientist Program. Her PhD thesis described the novel identification of a population of cancer stem cells that exclusively drive the formation of brain tumours. Since 2007, Dr. Singh’s lab applies a developmental neurobiology framework to the study of brain tumorigenesis. Building upon previous cell culture techniques developed for the isolation of normal neural stem cells (NSC) and applying them to brain tumours, and through development of a xenograft model to efficiently study brain tumour initiating cell (BTIC) activity, Dr. Singh’s lab aims to understand the molecular mechanisms that govern BTIC self-renewal. Dr. Singh is currently studying the regulation of BTIC signaling pathways in glioblastoma, brain metastases and childhood medulloblastoma, with an ultimate goal of selectively targeting the BTIC with appropriately tailored drug and molecular therapies. Her laboratory is funded by CCSRI, CIHR, TFRI, CRS, the Stem Cell Network, McMaster Surgical Associates, Brain Canada and the Boris Family Fund.

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