How a Broken Enzyme Could Open New Paths for Ovarian Cancer Treatment

What issue did you address in your research and what did your studies find?

Ovarian cancer remains difficult to treat because cancer cells can detach from the primary tumor and spread throughout the abdominal cavity. Due to this pattern of spread, patients with ovarian cancer are often diagnosed at an advanced stage and may have aggressive disease. My research focused on understanding the biology behind ovarian cancer progression by studying a protein called PRSS23, which was previously thought to function as an enzyme and repeatedly appeared in patient datasets as a predictor of poor survival.

Using a combination of biochemical approaches, computational structural analysis and preclinical models, I investigated how this protein contributes to cancer progression. What we found was unexpected: although PRSS23 resembles a protease, a type of enzyme that typically acts like molecular "scissors" to cut other proteins, it lacks a key mechanism normally needed to activate this cutting function. In other words, it may look like molecular scissors, but it does not appear to be able to cut.

To determine whether PRSS23 could still influence cancer progression despite lacking a key mechanism needed for its enzymatic activity, we engineered a version of PRSS23 designed to prevent catalytic activity and compared its effects with those of the normal protein. Cancer cells behaved the same in both cases, continuing to grow, survive and resist cell death. This provided evidence that PRSS23 promotes tumor progression through a mechanism independent of enzymatic activity.

Together, these findings suggest that a protein long assumed to be an enzyme may instead be a disabled enzyme or a pseudoprotease (a "false" protein cutter) and yet still play a critical role in aggressive tumor biology. This opens new directions for identifying therapeutic targets by focusing not only on proteins that carry out chemical reactions, but also on those that influence cellular behavior in other ways.

How did Mayo Clinic shape your development as a scientist?

Mayo Clinic has a culture that is distinctive in one important way: the patient is never abstract. Even in a basic science laboratory studying molecular mechanisms, you are surrounded by people who care for patients every day. That proximity changes how you think about your work. It keeps the stakes real and reinforces what actually matters.

That perspective is paired with a training environment that emphasizes rigor, integrity and purpose. I developed the ability to question results carefully, design experiments thoughtfully and approach science with a level of precision that prioritizes accuracy over convenience. At the same time, Mayo's investment in developing scientists as people, not just as producers of data, has shaped how I think about the broader impact of this work beyond publications.

What's next?

Before beginning my Ph.D., I spent almost a decade at Mayo Clinic as a research technologist working in translational science as a clinical research coordinator, contributing to several clinical trials and research studies involving blood cancers. This experience gave me a first-hand understanding of bench-to-bedside-and-back. Seeing firsthand how research impacts patients motivated me to pursue doctoral training and ask my own scientific questions.

Following my defense, I am continuing at Mayo Clinic as a research fellow, where I will focus on investigating understudied proteins similar to PRSS23 that contribute to the progression of kidney cancer and small cell lung cancer.

In the long term, I aim to work in an environment where fundamental discoveries can be translated into clinical advances. No matter the setting, I will continue to focus on what the data shows and how that knowledge can be used to improve outcomes for patients.

This article was written by Lizz Cervantes, a Ph.D. candidate in Clinical and Translational Science at Mayo Clinic Graduate School of Biomedical Sciences.