UW professor tackles cancer treatment with new approach

A quarter century ago, Wayne Brodland was a PhD candidate for civil engineering at the University of Manitoba. After meeting Richard Gordan, a biologist in search of an engineer to help build models to study neural tube closure, Brodland embarked on a lifetime of research that has taken on higher goals with every discovery.

“[Gordan] and I worked together for about eight years and we got well on our way toward studying neural tube closure,” said Brodland.

“Early in development — in humans it’s about day 26 — there’s a sheet of tissue called the neural plate and it needs to roll up to become a tube. That tube becomes a precursor to the spinal cord and brain. The most common human birth defect is spina bifida, which occurs when the tube does not close properly along its entire length,” said Brodland, speaking about his first research project.

“We’ve been studying the forces that cause the cells in the neural plate to move in just the right way to form the neural tube, and our focus has been on the forces that are exerted between cells, because cells cannot move unless forces are exerted … It took us 25 years to figure out how the neural plate actually rolls into a tube,” said Brodland

Once the work on the neural plate was finished, it was discovered that the information yielded by the 25 years of computational models for understanding cells, tissues and embryos which Brodland developed with the help of his students could be put to another use.

“We’ve been using all of the cell and tissue movement information to study neural tube formation, and recently we’ve been applying the same tools to wound healing and cancer,” Brodland said.

Ninety per cent of cancer deaths are caused by metastasis, which is defined as the development of secondary malignant growths at a distance from the primary site of the cancer.

According to Brodland, if the secondary cells did not metastasize, doctors would simply be able to surgically remove the cancer, and, assuming that they remove it entirely, the average patient would be able to recover, cancer-free.

“[Secondary cancer cells] get into either the bloodstream or the lymph system, they get carried to other parts of the body, they exit the vessel and they start a secondary tumour in a different location,” Brodland said. “There are usually tens of these secondary cells and so … it’s not practical to remove [the secondary tumours they cause] by surgery and they have to rely on chemotherapy or radiation, but at that point it’s quite serious.

“We’ve been studying the mechanics of what causes a cell to move and that’s why our research works well with cancer research … If we could stop cells from leaving the surface of the tumour, then we could stop metastasis and prevent 90 per cent of cancer-related deaths,” Brodland said.

“We want to look at the exact process by which the cell leaves the primary tumour, and using our models, we can try out various ideas. Suppose we can make a drug that affects the forces that allow the cell to leave the primary tumour,” Brodland said. “With our models we can begin to play with how to change these properties so that the cell can’t escape the tumour.”

Brodland hopes that through work with an experimental collaborator, he and his team will be able to help turn their research into a marketable drug that can help doctors treat their cancer patients.

Brodland, who has had trouble getting the medical community to pick up some of his previous discoveries, said, “I realized that we needed to directly engage the medical community and sell what we had learned so they would see the value of what we had done, and we didn’t do that very effectively [last time].

“I think with cancer we’re going to be very focused on making sure the things we learn get properly communicated to the medical community,” Brodland said.

Despite having started on a mission to learn how the neural tube works, Brodland says that cancer research has become his new focus.

“I’ve had too many friends and family members affected by cancer and I would really like it if we could find a way to prevent cancer metastasis,” he said.

“We’re taking a risk by looking at something like this, but at this point in my career I can afford to do that,” Brodland said.

“I’ve been very privileged to work at the University of Waterloo and have really bright students, some of them undergraduates, some of them graduates, work in my lab and make really important contributions. They’ve encouraged us along in our work [and] my lab would not have made the discoveries it has were it not for the key contributions made by students.”