Researcher ‘piecing the puzzle together’ on ovarian cancer therapies

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 Ph.D. 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, in order to develop novel biomarkers and therapies. The goal is that this information will be used to help develop targeted therapies and improve the lives of women diagnosed with this disease.

Jessica McAnulty, a doctoral 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 potentially kill HGSC cells and not normal cells. 

McAnulty in Lab

Vital research

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

While in Dr. Analisa DiFeo’s laboratory, McAnulty identified a potent cancer-specific compound, DL78, through a combination of research techniques and uncovered it affects ovarian cancer cells but not normal cells. 

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 to answer different questions. 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 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 bodies undergoes 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 uncontrolled 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. The division defects induced by DL78 ultimately lead to death of the cancer cells.

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 mouse 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. 

Researchers now have an unprecedented number of scientific tools at their disposal to pursue new potential targeted therapies for ovarian cancer patients.

What is known is that Michigan Medicine researchers and Ph.D. students like McAnulty will be leading the way.