Ovarian cancer is among the most lethal precisely because it hides until it has already spread, and the treatments that follow are blunt instruments that harm as much as they heal. Researchers at the University of Maryland, Baltimore County have now identified an enzyme called USP15 that ovarian cancer cells rely on to survive and proliferate — and whose suppression, in laboratory and animal studies, slows tumor growth while making cancer cells more vulnerable to existing chemotherapy drugs. The discovery, rooted in a chance observation about a mutant protein that drives rather than suppresses
USP15 enzyme identified as promising ovarian cancer drug target
Cancer cells were still growing, but struggling to divide
Mark
So ovarian cancer is diagnosed late most of the time—that's the core problem here?
Mimi
It's one of them. By the time it's caught, it's usually spread, and survival rates drop sharply. But even when treatment works, it damages healthy cells too.
Luke
Right, so the question is whether USP15 is actually a better target than what doctors are already using.
Mimi
That's what the research suggests. Cancer cells seem to depend on USP15 more than normal cells do. When you reduce it, growth slows and the cells become more vulnerable to existing drugs.
Mark
More vulnerable how? Does that mean smaller doses?
Mimi
Potentially. The cells became more sensitive to carboplatin, paclitaxel, and doxorubicin. If lower doses achieve the same effect, that's less toxicity for the patient.
Luke
But this is all in cells and mice, right? We don't know yet if it works in human patients.
Mimi
Correct. That's the next hurdle. They need to figure out how to safely inhibit USP15 in living people.
Mark
Do those inhibitor molecules exist?
Mimi
Yes. Lab versions already do. That's actually encouraging—it means there's a starting point for drug development.
Luke
How long before this becomes a treatment someone can actually receive?
Mimi
That depends on pharmaceutical interest and clinical trial timelines. Years, probably. But the foundation is there.
Mark
And if it works, what changes for patients?
Mimi
Potentially lower doses of chemotherapy with the same benefit. Less damage to healthy tissue. Better quality of life during treatment.
O Pulso
- Ovarian cancer kills most of its patients because it is diagnosed late and treated with chemotherapy that damages healthy tissue alongside malignant cells — a problem that has persisted for decades.
- A chance observation during postdoctoral research revealed that a common cancer-driving mutation doesn't just break a cellular brake — it jams the accelerator, and an enzyme called USP15 is what keeps that accelerator stuck.
- When researchers reduced USP15 levels in cancer cells and mice, tumors grew more slowly, chromosomes fractured during cell division, and the cancer's ability to spread to other tissues diminished.
- Critically, cancer cells with less USP15 became significantly more sensitive to standard chemotherapy drugs, raising the possibility that lower, less toxic doses could achieve the same therapeutic effect.
- Inhibitor molecules targeting USP15 already exist in research settings, giving pharmaceutical developers a concrete starting point to pursue clinical treatments within a realistic timeframe.
Ovarian cancer is among the most lethal precisely because it hides until it has already spread, and the treatments that follow are blunt instruments that harm as much as they heal. Researchers at the University of Maryland, Baltimore County have now identified an enzyme called USP15 that ovarian cancer cells rely on to survive and proliferate — and whose suppression, in laboratory and animal studies, slows tumor growth while making cancer cells more vulnerable to existing chemotherapy drugs. The discovery, rooted in a chance observation about a mutant protein that drives rather than suppresses cancer, points toward a future in which treatment might be made more precise and less punishing.
Ovarian cancer is a disease defined by lateness — most diagnoses arrive only after the cancer has already spread, leaving fewer than three in ten patients alive five years later. The chemotherapy that follows works, but indiscriminately, and researchers have long sought a more targeted approach. A team at the University of Maryland, Baltimore County believes they may have found one.
The discovery traces back to a postdoctoral observation by Achuth Padmanabhan, now an assistant professor at UMBC, who was studying p53 — a protein that normally suppresses tumor formation. He found that in nearly all aggressive ovarian cancers, p53 mutations don't simply disable the protein; they transform it into an active driver of cancer growth. Worse, this mutant form lingers far longer than it should. The reason, he determined, was USP15, an enzyme that strips the molecular tags that would otherwise mark proteins for destruction.
When Padmanabhan established his own lab, doctoral student Ayokunnumi Ogunsanya took up the broader question of what USP15 does in ovarian cancer. Working in cell cultures and mouse models, the team found that reducing USP15 triggered a cascade of damaging effects in cancer cells: slower growth, chromosomal failures during cell division, diminished ability to invade other tissues, and — most promisingly — heightened sensitivity to existing chemotherapy drugs including carboplatin and paclitaxel. The implication is that lower, less toxic doses might achieve the same results.
The path was not without complications. Some early results defied expectation, and the team had to repeat experiments and reframe their questions before understanding that cancer cells with reduced USP15 were still dividing — just failing to complete the process cleanly, leading to lethal chromosomal damage.
The next steps involve understanding what regulates USP15 in cancer cells and whether its suppression might also alter the tumor's surrounding environment. The translational leap to human medicine remains significant, but Padmanabhan points out that USP15 inhibitor molecules already exist in research settings — a foundation that could draw pharmaceutical interest and bring this line of inquiry closer to patients.
Ovarian cancer arrives late. By the time most women receive a diagnosis, the disease has already migrated beyond the ovaries to other organs—and at that stage, fewer than three in ten patients survive five years. The standard treatments that oncologists reach for work, but they work indiscriminately, poisoning healthy tissue alongside malignant cells. A team at the University of Maryland, Baltimore County has identified a potential way around this problem: an enzyme called USP15 that ovarian cancer cells depend on far more heavily than normal ones do.
The discovery emerged almost by accident. Achuth Padmanabhan, now an assistant professor at UMBC, was working as a postdoctoral fellow at Baylor College of Medicine studying p53, a protein that normally acts as the body's brake on tumor formation. He noticed something troubling in ovarian cancer cells: mutations in the p53 gene—which occur in nearly every case of the most aggressive form of the disease—don't simply disable the protein's protective function. Instead, two-thirds of these mutations transform p53 into something worse: a stuck accelerator that actively drives cancer forward, and one that lingers in the cell far longer than it should. Padmanabhan traced this persistence to USP15, an enzyme that removes molecular tags marking proteins for destruction. When USP15 is abundant, mutant p53 proteins escape their scheduled demolition and continue fueling cancer growth.
When Padmanabhan moved to UMBC in 2019, he decided to investigate whether USP15 played a broader role in ovarian cancer beyond stabilizing mutant p53. Ayokunnumi Ogunsanya, a doctoral student who joined his lab in 2021, took on the question as the centerpiece of her research. Working in both cell cultures and mice, the team discovered that reducing USP15 levels produced a cascade of effects that made it an attractive drug target. Cancer cells grew more slowly. Their chromosomes failed to separate cleanly during division, causing DNA damage that killed the cells. Their ability to migrate and invade other tissues diminished. And critically, they became more sensitive to the chemotherapy drugs already in use—carboplatin, paclitaxel, and doxorubicin. The findings, published in September in Molecular Therapy Oncology, suggested that lower doses of existing drugs might achieve the same therapeutic effect with substantially less toxicity to the patient.
The path to these conclusions was not straightforward. Early experiments produced unexpected results. One molecule that typically rises with cancer progression fell instead when USP15 was reduced. Rather than accept the anomaly, Ogunsanya and her colleagues repeated the work and approached the problem from multiple angles. They discovered that a different marker of cell division did decline as expected, suggesting that cancer cells with less USP15 were still growing but struggling to complete the division process. That observation led them to identify the specific failure: cancer cells could not properly separate their duplicated chromosomes during mitosis.
The next phase of research will focus on the basic mechanics of USP15 itself—what controls its levels in cancer cells, and whether reducing it might also reshape the tumor microenvironment in ways that enhance treatment. The practical challenge of translating these findings into human medicine remains substantial. Yet Padmanabhan notes that laboratory molecules capable of inhibiting USP15 already exist, providing a foundation for pharmaceutical development. The hope is that this work will attract drug companies and other research groups to pursue the development of USP15 inhibitors that could eventually reach patients.
Citações Notáveis
Mutated p53 enhances cancer progression, and it also sticks around in the cell much longer than normal.— Achuth Padmanabhan, assistant professor at UMBC
The additional experiments strengthened the story and gave us greater confidence in the findings.— Ayokunnumi Ogunsanya, doctoral researcher
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