Drs. Rama Khoka (L) and Barbara Grünwald have published new research which illustrates how the complex tumour micro-environment inside of pancreatic cancers organizes itself to promote aggressive progression and treatment resistance. (Photos: UHN

Princess Margaret Cancer Centre researchers have discovered how the complex tumour micro-environment inside of pancreatic cancers organ​izes itself to promote aggressive progression and treatment resistance.

The PM team have made the discovery by delving into the powerful network of normal body cells which are hijacked by cancer to support the tumour. The new study breaks down how this network establishes “functional units” that make key contributions to pancreatic cancer and its clinical outcome.

The results were published recently in the journal Cell. Drs. Rama Khokha, Thomas Kislinger, Steven Gallinger and Melanie Boerries are co-senior authors of the interdisciplinary study.

Pancreatic cancer often grows quickly and has a poor prognosis – just eight per cent of people diagnosed with it will survive for more than five years.

Those grim statistics highlight the need to better understand the peculiar and extraordinarily complex biology of pancreatic tumours. The work, from the lab of Dr. Khokha, PM Senior Scientist, complements the findings of multiple recent studies on the vast cellular diversity of pancreatic cancer by building an integrative framework to understand its micro-environment.​

That, in turn, could improve the science of pancreatic cancer research and help pave the way for precision medicine, says study first author, Dr. Barbara Grünwald.

“We hope this will lead to a refinement of the so-far futile strategies for identification of urgently needed biomarkers and new therapeutic targets,” says Dr. Grünwald, a post-doctoral researcher at the Princess Margaret.

Dr. Grünwald says the research could also help clinicians bring data on the tumour micro-environment into decision-making when it comes to patient treatments.

“The tumour micro-environment is very influential in the disease course,” she says. “But because of its complexity and heterogeneity, it's not informing any clinical decision-making right now.”

Dr. Khokha says the study’s deep analysis moves the field of pancreatic tumour research forward.

“Just as pancreatic cancer is notoriously lethal, its’ tumor micro-environment’s complexity is equally notorious,” she said. “This study shows how this tumour complexity is actually well-ordered, how the cells inside it build communities and how they self-organize into functional units.

“This brings a lot of clarity to the field.”

Dr. Grünwald praises the team science that led to this work, something made possible by the collaborative culture at the Princess Margaret.​

“Research groups and clinical teams from Canada and Germany also worked together across disciplines,” she said. “It’s amazing to see what team science can achieve.”

This work was supported by the Princess Margaret Cancer Foundation, Canadian Cancer Society, Ontario Institute for Cancer Research, Terry Fox Research Institute, the Government of Ontario, Wallace McCain Pancreatic Cancer Centre, and Pancreatic Cancer Canada Foundation.
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