Microscopic view of cancer cells: A collaborative effort among Oregon Health & Science University and three other universities has led to the development of mathematical models that may enhance our understanding of how these cells respond to various cancer therapies. This groundbreaking research, published in the journal Cell, aims to pave the way for digital models that can predict cell behavior, revolutionizing treatment strategies for cancer. (Getty)
A collaboration among Oregon Health & Science University and three other universities has produced mathematical models that could begin to unlock how groups of cells will respond to various cancer therapy combinations.
Laura Heiser, Ph.D. (OHSU)
The findings, published today in the journal Cell, have broad implications across cancer-related specialties, giving researchers the keys to developing digital models designed to test and predict cell behavior.
“That’s the long-term goal,” said Laura Heiser, Ph.D., vice chair of biomedical engineering, OHSU School of Medicine, and associate director of complex systems modeling in the Cancer Early Detection Advanced Research Center program, OHSU Knight Cancer Institute.
“This research gives us a tool to begin to predict multicellular behavior. We’re not there yet, but it puts us firmly on the road to being able to identify treatment combinations predicted to work best across cancer types, enabling development of novel treatment strategies.”
Being able to do this, and do it as soon as possible, is critical for patients with cancer. Customized treatments, also called personalized or precision medicine, deliver better results, fewer side effects and hopes for improving clinical outcomes.
Young Hwan Chang, Ph.D. (OHSU)
Heiser and Young Hwan Chang, Ph.D., associate professor of biomedical engineering, School of Medicine, and Knight Cancer Institute Interim Director Lisa Coussens, Ph.D., collaborated with researchers from Indiana University, University of Maryland and Johns Hopkins University. In all, four OHSU faculty members and two graduate student trainees took part in the research.
A Grassroots Effort
The effort began in 2020, when Heiser and Chang were conducting research into mechanisms of therapeutic resistance in breast cancer and began collaborating with Paul Macklin, Ph.D. A researcher from Indiana University, Macklin is the lead developer of PhysiCell, a software designed to create computational models of cells and tissues.
Macklin already had ongoing collaborations with Elana Fertig, Ph.D., from University of Maryland, who was focused on pancreatic cancer, and Johns Hopkins University’s Genevieve Stein-O’Brien, Ph.D., who was researching brain development. In other studies, Fertig collaborated with Coussens to understand epigenetic mechanisms impacting therapy response in breast cancer regulated by macrophages, a type of immune cell.
Thanks to philanthropic and National Institutes of Health funding, the multi-institutional group of scientists began collaborating to harness the various scientific approaches across their five labs.
For the last two years, they have been meeting every Friday to present their findings and share updates. Their goal? To develop rational rules based on significant biologic responses, which could then inform mathematical prediction models for therapy responses.
Read more about the Knight Cancer Institute in this media kit.
For Heiser, the Friday meetings became a highlight of her week.
“I would really look forward to them,” she says. “I think we all became very invested in the time spent and in the commitment, we had to each other and to developing our ideas.”
Using validated preclinical biology, the group was able to develop and replicate computational models for cells in multiple types of cancer — a milestone and a moment when the group knew they had a novel approach that could significantly impact patients with cancer.
“There wasn’t one a-ha moment; there were many. It was a very grassroots effort,” Heiser said. “And we were fortunate to be able to build off of strong research that already existed within OHSU’s biomedical engineering and cancer biology-focused departments and within the Knight Cancer Institute.”
The group leveraged the following:
- Twenty years of in vivo breast cancer modeling in the Coussens Lab, which demonstrated that a group of immune cells called macrophages and T cells significantly impact how cancer cells progress into lethal tumors.
- 2022 research from the Heiser Lab, which developed a detailed map of how breast cells respond to extracellular signals. This helped create a computational model — a test done on a computer instead of in a lab — to better understand how those cells behave.
- Research from the Chang lab, focused on developing advanced analytics for imaging data.
The findings open the door for next steps — new research questions that now can be asked and answered with greater accuracy and speed.
Lisa Coussens, Ph.D. (Courtesy)
“The collaboration and team-science approach provides a foundational platform to predict the effects of various cell types embedded within tumors expressing different therapeutic targets, based on biological findings, without having to do 20 years’ worth of in vivo biological studies,” Coussens said.
For Heiser and the entire group, working together from a multidisciplinary standpoint has been not only effective, but gratifying.
“We really need a multidisciplinary view if we’re going to cure cancer,” Heiser said. “Our ultimate goal is always to improve outcomes for patients, and to do that, we have to tackle these questions from many different angles.
“It’s a multifaceted disease, so it makes sense that the approach needs to be multifaceted as well. We have been able to demonstrate that the work we’ve been doing these past several years and over these many Fridays has yielded something that can be useful to the broader cancer research community, and that is really very meaningful.”
Research reported in this publication was supported by the Jayne Koskinas Ted Giovanis Foundation for Health and Policy, the National Foundation for Cancer Research and the Susan G Komen Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the various foundations.