[2023-10-30] Solving the puzzle of ovarian cancer

In response to my recent post on the Ovarian Cancer Canada Board of Directors, a friend sent me a link to an episode of The Ottawa Hospital Foundation's podcast Pulse featuring Dr. Barbara Vanderhyden (Episode 89: Unlocking discoveries in ovarian cancer). Dr. Vanderhyden is a senior research scientist with the Ottawa Hospital Research Institute and the Corinne Boyer Chair in Ovarian Cancer Research at the University of Ottawa. She spoke with Pulse host Shelley McLean in September.

Dr. Vanderhyden noted that when she joined The Ottawa Hospital's Cancer Therapeutics Program in 1991, there were very few people doing research into ovarian cancer in Canada. She said that she saw an opportunity to specialize in an area of research that needed attention, especially after seeing patients waiting for their cancer treatments in The Ottawa Hospital's Cancer Centre. She thought, "I need to do more for them. Simply looking at ovarian function wasn't enough. I need to start thinking about ovarian cancer."

In fact, patients are so central to the research being conducted at the Vanderhyden Lab that they are considered unofficial members of the team. Dr. Vanderhyden said:

The unofficial members of our team are always the cancer patients, and particularly the ovarian cancer patients. We connect with them at every opportunity. We let them know about our research. And we listen to their ideas because they're the ones who are truly going to tell us what the experience is, what worked for them, and what particularly did not work for them. And we try to move in if there are things that we can do to address the problems that they've had.

Dr. Vanderhyden heaps praise upon her team members, identifying in particular Elizabeth Macdonald, a research technician who has been with her since 1995. She described the focus of their research in this way:

We want to know how and why the cancers begin, because that will give us a better idea of how we can stop it from happening. And if we can't stop it from happening, then what can we do to make sure there are...effective treatments available that will prevent the tumour from progressing further, and, ideally, down the road, have something that will ideally cure the ovarian cancer.

She described two scientific breakthroughs that she and her team have achieved in the past few years:
  1. Mechanism to help immune cells recognize ovarian cancer tumours. Dr. Vanderhyden said that they know from clinical trials with ovarian cancer patients that they generally do not respond to immunotherapy. "It would seem that the ovarian tumours are really, really effective at shutting off all the mechanisms that would normally be used by the immune system to see them, to destroy them. The tumours just shut that off, and so they can't be seen by the immune cells. And so even if there's a really effective immunotherapy in other types of cancers, when it's given to an ovarian cancer patient, the immune cells cannot see the cancer cells that they're supposed to destroy. So we thought how do we make the ovarian cancers recognizable? How do we make them visible to the immune system?" They discovered the linchpin that can turn the mechanism back on and make ovarian tumours recognizable to immune cells. They're at the preclinical trial stage now. Dr. Vanderhyden credits Galaxia Rodriguez with developing this strategy.
  2. Discovery that human ovaries become fibrotic as people with ovaries age and that a diabetes drug prevents this aging. "We made the serendipitous discovery that human ovaries, as women age, become fibrotic." An Ottawa Hospital article describes fibrosis as "the natural stiffening of the ovaries." There was one exception in the data: a woman who had been taking the drug Metformin for diabetes. Her ovaries had not aged and did not become fibrotic. Additional data from other women who had taken Metformin as well as a large research study with mice confirmed that people and mice given Metformin do not develop ovarian fibrosis with age. Dr. Vanderhyden added, "Now we have some sense of what is contributing to the cancer's being able to grow so readily in ovaries, and we have a way to stop it." She and her team are now working with clinicians to figure out how to apply this research, especially in people with mutations in their BRCA1 and BRCA2 genes. They are looking to answer the following question: can metformin slow down ovarian fibrosis in women with BRCA1 or BRCA2 mutations or even prevent it entirely so they have a much reduced risk of developing ovarian cancer. Dr. Vanderhyden noted that Curtis McCloskey made the discovery of ovarian fibrosis.

You can hear the excitement Dr. Vanderhyden has for her work. She mentioned that it's only in the last few years that there have been new treatments for ovarian cancer. With an increased body of people doing ovarian cancer research in Canada and all the advances being made, the hope for new treatments is high, she said. She also spoke with excitement about having recruited a new young scientist, David Cook, who will start in January. His skill set is bioinformatics. "He gives us the opportunity to look at ovarian cancer from another different perspective that none of us here have." (Shelley McLean interviewed David Cook for Pulse: Episode 23: From rock star wannabe to rock star researcher.)

Shelley McLean concluded her interview by asking Dr. Vanderhyden what she does to unwind when she's not in the lab. The research scientist said:

I love to solve puzzles. So solving puzzles is what I do in the evenings when I try to unwind. So Sudokus or Wordles or jigsaw puzzles of any kind. I'm also a big reader. Mysteries will always be my favourite; clearly that's a puzzle to solve."

I smiled at this. I, too, love solving puzzles. My daughter and I do The New York Times Wordle, Mini-Crossword and Connections games every morning at breakfast. I've recently learned how to do hard Sudoku puzzles, thanks to Mel. And I've always loved jigsaw puzzles and murder mysteries.

I wasn't aware of The Ottawa Hospital's podcast before my friend sent me the link a few days ago. Pulse is easy to listen to, and it was fascinating to learn more about the work of Dr. Vanderhyden and her team and the promising discoveries they're making.