Under the Microscope: Protecting fertility during cancer treatment

When a child falls ill with cancer, most families focus on getting through the next few months, with little energy to spare for thinking decades into the future. But the quick and difficult decisions made during cancer treatment can have lasting effects.

Case in point: Fertility. Up to 20% of young girls and women undergoing cancer treatment experience damage to their ovaries and egg supplies. Egg freezing is one of the few options available to these patients, but the process can delay cancer treatment and is difficult to perform in girls who haven’t reached puberty.

Ewelina Bolcun-Filas, Ph.D., from The Jackson Laboratory in Bar Harbor, Maine, is working to find better ways to protect the reproductive health of cancer patients. While researching the causes of infertility, Bolcun-Filas and her team previously discovered fertility in mice could be protected from radiation damage by turning off the gene that codes for a protein known as CHK2.

Photo by Tiffany Laufer, The Jackson Laboratory.

“I realized that if we could understand this process better, it might lead to a way to protect reproductive health in patients undergoing radiation treatment without the need to freeze eggs,” she said. “Even though it wasn’t what I had been studying at the time, I felt it was important to refocus my research on something that could help improve the lives of cancer survivors.”

Blocking a problematic protein

With V Foundation funding, Bolcun-Filas is trying to find ways to block CHK2. “Inhibitors for CHK2 and a similar protein known as CHK1 already exist because researchers are studying them as cancer therapy sensitizers,” she said. “This could mean that one treatment strategy could protect eggs and help fight cancer, creating a win-win.”

The researchers have tested different inhibitors for CHK2 and found one that can also protect eggs. However, they found this inhibitor caused unwanted side effects because it also acts on CHK1.

“We know that eggs can be protected by genetically inhibiting CHK2, but we don’t want to induce new side effects to treat a side effect of cancer therapies,” said Bolcun-Filas. “More research needs to be invested in modifying the promising inhibitor to minimize side effects or in finding another way to achieve the same inhibition without inducing other toxicities.”

Bolcun-Filas is working to better understand how chemotherapy and radiation damage the ovaries by using some of the newest single-cell RNA sequencing techniques to identify proteins that might be involved in the process. Her lab is also taking advantage of a unique resource at The Jackson Laboratory — genetically diverse mice. Unlike the genetic clones used in most mouse research, these mice mimic the human population in that every mouse has somewhat different genetic characteristic that make it unique.

“We are learning that, similar to what is seen in humans, not every mouse is affected the same way by radiation or chemotherapy,” said Bolcun-Filas. “When we find that one mouse is more resistant to toxicity, we can then take a look at what makes that mouse more resistant. Harnessing this knowledge could lead to new treatment strategies and predictive risk markers.”

The V Foundation funding allowed me to build up preliminary data that will make us more successful in obtaining grants moving forward.

Ewelina Bolcun-Filas, Ph.D.

Focusing on cancer survivors

While protecting the long-term health and quality of life of cancer survivors is an integral part of winning the fight against cancer, Bolcun-Filas points out that it has historically been difficult to obtain funding for cancer research that isn’t aimed at finding a cure. She’s thankful this seems to be changing.

“I’m seeing more funding opportunities in this area and more recognition that reproductive health is important to cancer survivors,” said Bolcun-Filas. “The V Foundation funding allowed me to build up preliminary data that will make us more successful in obtaining grants moving forward.”

She also attended a V Foundation retreat where she learned how to better communicate about her research to lay audiences. “I found this training very useful,” said Bolcun-Filas. “I applaud the V Foundation for teaching a group of scientists to communicate science to others who are not experts in the field.”