The 30% Survival Stat That Needs a New Recipe: Why an Enzyme Named USP15 Could Fix Ovarian Cancer Treatment
New research points to a molecular target that might spare healthy cells during aggressive ovarian cancer therapy.
We all know that in the kitchen, you do not just throw ingredients together. You have to understand exactly what each component does to the final dish. When it comes to our bodies, we often treat them like a machine that just runs until something breaks. But what if the key to fixing a broken machine is a hidden ingredient that has been sitting right there the whole time? New research from the University of Maryland, Baltimore County (UMBC) suggests that we might have found such an ingredient for treating ovarian cancer. It is an enzyme called USP15, and scientists believe it is the target we have been looking for.
Ovarian cancer is a difficult diagnosis to manage. It is frequently diagnosed after it has already begun to spread to other parts of the body. At that stage, the five-year survival rate drops below 30 percent. That is a sobering statistic for anyone trying to cook up a plan for recovery. Furthermore, standard therapies used to fight this disease are not very precise. They tend to cause substantial harm to healthy cells alongside the cancerous ones. Think of it like using a flamethrower to light a candle. It gets the job done, but the heat damages everything else in the room. There has to be a better way to target only the bad guys.
Ayokunnumi "Ayo" Ogunsanya, a Ph.D. student in Achuth Padmanabhan's research group, is the lead author on a new study. This work, published in Molecular Therapy Oncology, offers a potential solution to that problem. The study focused on a molecular target for new cancer drugs. The goal was to find a way to treat ovarian cancer without causing collateral damage. The results show that USP15 is a prime candidate for this role because ovarian cancer cells appear to rely on it more heavily than normal cells.
The story of this discovery began serendipitously. Much of great science starts this way. As a postdoctoral fellow at Baylor College of Medicine, Achuth Padmanabhan was studying the protein p53. In its normal form, this protein helps prevent tumor formation. It acts like the body's natural brakes on cancer progression. However, mutations in the gene that codes for p53 occur in nearly every case of the most common and lethal form of ovarian cancer.
Here is where the research gets interesting. Typically, you would assume that a mutation would disrupt the function of a tumor suppressor. But Padmanabhan discovered that two-thirds of p53 mutations in ovarian cancer actually do the opposite. They do not just disable the brakes; they convert them into a stuck accelerator. The mutated p53 enhances cancer progression and sticks around in the cell much longer than normal. It is a relentless force driving the disease forward.
On further investigation, Padmanabhan found that the enzyme USP15 was the one stabilizing this particular p53 mutant. This was a crucial clue. USP15's function offered a clear explanation for why this was happening. The enzyme removes small molecular "tags" attached to proteins that label them for degradation. So when there is a lot of USP15 around, fewer mutant proteins remain marked for destruction. The bad stuff just stays longer and causes more harm.
When Padmanabhan returned to UMBC as an assistant professor in 2019, he set out to explore what broader role USP15 might play in the body. Ogunsanya joined Padmanabhan's lab in 2021, and she has made exploring the role of USP15 in ovarian cancer the core of her Ph.D. "I'm very excited about these findings, as they provide new insight into how USP15 contributes to ovarian cancer progression," she says. The team conducted experiments in cells and in mice to test their theories.
The results of these experiments were quite telling. Lowering USP15 levels causes a constellation of effects that make it a prime target for new treatments. It slows cancer-cell growth, prevents chromosomes in cancer cells from separating cleanly during division, and reduces the cells' ability to migrate and invade other tissues. Perhaps most importantly, it makes cancer cells more sensitive to common chemotherapy drugs.
This last point is vital for patients. With less USP15 present, lower doses of these drugs might achieve the same treatment effect with less toxicity. The team looked at common ovarian cancer treatments like carboplatin and paclitaxel. They also looked at doxorubicin, a particularly toxic drug used for a range of cancers. Reducing USP15 levels made these drugs work better against the cancer.
Yet reaching their conclusions was not always straightforward. "Some of our early findings weren't what we anticipated, so we repeated experiments and approached the questions from multiple angles," Ogunsanya explains. This process of repetition is what separates good science from guesswork. For example, a molecule that usually tracks with cell growth rose instead of falling in the presence of reduced USP15. On further investigation, the team discovered a different molecule associated with cell division that did go down. This combination suggested a specific type of struggle for the cancer cells.
That struggle led them to a specific discovery. With less USP15, cancer cells were growing but struggling to divide successfully. They were failing to properly separate their duplicated chromosomes during cell division. This failure leads to DNA damage and ultimately cell death. It is a critical mechanism that shows how delicate the balance inside the cell really is.
For those following this research, the future looks promising. Padmanabhan's team wants to further reveal USP15's basic functionality. They want to learn what controls USP15 levels in cancer cells. They also want to know if inhibiting the enzyme can reshape a tumor's immediate surroundings. Even with that information, the need to figure out how to reduce USP15 levels safely in human patients will remain. The good news is that molecules used to inhibit USP15 in laboratory experiments already exist. These could be a starting point for developing human drugs.
"Hopefully, work such as ours demonstrating the potential of USP15 as an anticancer therapeutic target will motivate pharmaceutical companies and other research groups to pursue the development of clinically translatable USP15 inhibitors," Padmanabhan notes. It is a hopeful outlook for a disease that has historically been so difficult to treat. The focus remains on practical solutions that can be translated to a hospital bed.
More information on this study can be found in the journal Molecular Therapy Oncology. The authors are Ayokunnumi Ogunsanya et al. You can view the study here. The research was supported by the National Institute of General Medical Sciences of the National Institutes of Health. This work illustrates the importance of persistence in scientific inquiry. Sometimes the path is not a straight line, but the destination is worth the journey.
First reported by Medical Xpress.
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