Researcher ‘piecing the puzzle together’ on ovarian cancer therapies

Approximately a 6-minute read.

Key takeaways:

• Graduate student Jessica McAnulty came to Michigan Medicine thanks to the organization’s strong focus on translational research.
• McAnulty and her colleagues in the DiFeo Lab are researching potential therapies for ovarian cancer.
• The lab’s promising findings will become a tool to better understand the molecular vulnerabilities of ovarian cancer. 

Jessica McAnulty has long been interested in biology. But it wasn’t until a summer internship with Merck, a multinational science and technology company, that she knew she wanted to be a scientist. 

Now, thanks to her experience as a graduate student here at Michigan Medicine, carrying out groundbreaking research with experts providing guidance and mentorship, she’s well on her way to leaving her mark on medical research and future cancer patients.

A tireless pursuit

Many diseases can stop us in our tracks — but perhaps few have as much of an emotional impact on patients and their families as cancer. That’s especially the case with ovarian cancer, which is the fifth leading cause of death by cancer in women in the U.S. 

As with many diseases, researchers at Michigan Medicine are working tirelessly to determine what causes ovarian cancer, what puts someone at greater risk for developing it and how to treat it once diagnosed. The DiFeo Lab at the U-M Medical School is one of the research groups studying genetic alterations that lead to gynecological cancers — specifically high grade serous cancer (HGSC), the most common subtype of ovarian cancer.

The goal is that this information will be used to help develop targeted therapies and improve the lives of women diagnosed with this disease.

McAnulty, a graduate student in the DiFeo Lab, is “working on piecing the puzzle together.” To do so, she is studying a novel drug, DL78, that was discovered to potently kill HGSC cells but not normal cells. 

Finding a home at U-M 

“When I started college at the University of Delaware, I was really excited about biology,” said McAnulty. “I wasn’t sure where it would take me though.”

Where it took her was a summer research opportunity with Merck. And after a successful experience that led to her gaining an understanding of the tools, technology and techniques to thrive in the lab, she was invited back for a second internship. 

“It was around this time that I met with colleagues over lunch to seek advice about graduate school,” McAnulty said. 

The various conversations with other scientists and mentors narrowed her list of schools she cared to apply to — leaving U-M near the top of the list. 

“U-M’s Molecular and Cellular Pathology Department has a strong focus on translational research, making it the perfect home for my Ph.D. pursuit,” she said.

Vital research 

Once in Ann Arbor, McAnulty’s efforts have led to groundbreaking findings. 

While in DiFeo’s laboratory, McAnulty identified a potent cancer-specific compound, DL78, through a combination of research techniques. 

First, ovarian cancer cells are collected from human tumor samples and cultured in the lab. Next, the cells are treated with DL78. At this point, a few different experiments may be conducted. For instance, to understand how specific genes and proteins are affected by the drug, RNA or protein are collected from the cells and studied. If a specific protein is found to be constitutively activated or in far higher quantities in cancer cells, for example, that could be instrumental in developing a targeted therapy.   

An example of this is Myc, a key regulator of many cell processes like cell growth and metabolism. It is also a protein that is highly expressed in more than 70% of human cancers. One of McAnulty’s especially exciting findings is that Myc may be affected by DL78. Historically, Myc was thought to be “undruggable” because of its protein structure, but findings like McAnulty’s are shedding new light on its potential as a drug therapy target. 

Another question important to answer is how many cells are in each stage of the cell cycle. Every dividing cell in our body undergoes some form of this cell cycle, which has different stages (some for growth, some for rest). Cancer, by definition, is “unchecked cell growth” and cancers may be characterized by mutations in different checkpoints along the cell cycle, allowing for continuous, unregulated growth. Ultimately, the end goal for any cancer researcher is to stop this proliferation and kill the cancer cells.

To date, McAnulty has found that DL78 prevents cancer cells from dividing by stopping them at a specific checkpoint in the cycle. Much like the arm of a railroad crossing can stop someone from going across the tracks, DL78 halts cancer cells from crossing the checkpoint and continuing to grow.

These experiments reveal a great deal of important information, and although the DiFeo Lab utilizes patient-derived cells, isolated cancer cells in a plastic Petri dish aren’t the same as cancer cells growing in a full organism. Further research and studies are necessary.

Next steps

McAnulty, the DiFeo Lab, and researchers around the world continue to work on novel approaches to treating ovarian cancer cells. 

For McAnulty, she continues to narrow in on DL78’s mechanism of action.

She hopes that future work, combined with her existing findings, will provide a clearer picture of DL78’s target within ovarian cancer cells.

Although McAnulty is careful to note, “my research shouldn’t be summarized as the next treatment for ovarian cancer, but instead as a tool to understand the molecular vulnerabilities of ovarian cancer.” 

It is an important reminder that bringing a new drug to the clinic takes years of research in cells, animal models, then humans to prove efficacy and safety. 

Fortunately, researchers now have an unprecedented number of scientific tools at their disposal to pursue new potential targeted therapies for ovarian cancer patients. And Michigan Medicine researchers and graduate students like McAnulty are leading the way.