When Alessandro Santin's team at Yale School of Medicine identified a cell-surface protein called Trop-2 on uterine cancer cells more than a decade ago, they glimpsed a possibility: what if they could design a drug to target that protein specifically, delivering chemotherapy directly to cancer cells while sparing healthy ones? That theoretical promise has now become clinical reality. Research published May 14 in Clinical Cancer Research shows that sacituzumab govitecan—a breast cancer drug already approved by the FDA—shrinks tumors in nearly three in ten treatment-resistant uterine cancer patients, offering hope to people who have exhausted standard options.
Uterine cancer is the deadliest cancer of the female reproductive system, and most patients face an existential problem: surgery and chemotherapy remain the backbone of treatment, but they don't work for everyone. Those who fail first-line therapies have historically been left with few paths forward. This matters urgently because the disease is becoming more common. The National Institutes of Health estimates that about 68,000 Americans will be diagnosed with uterine cancer in 2026, with approximately 14,400 expected to die from it. That number is projected to double by 2030—a crisis made worse by the fact that, unlike colon and breast cancer, uterine cancer is not part of standard screening programs.
In the Phase II trial, Santin and his colleagues recruited 50 patients with uterine cancer who had already failed standard chemotherapy and surgery. These patients received sacituzumab govitecan, administered intravenously in two doses every 21 days. The results were striking: 14 patients—28 percent of the group—showed a 30 percent or greater reduction in tumor size. Even more broadly, over 70 percent of all patients experienced some degree of tumor shrinkage. This effectiveness stands in sharp contrast to most chemotherapy treatments at this advanced stage of disease, which typically produce clinical responses in fewer than 15 percent of patients.
Santin, a professor of obstetrics, gynecology, and reproductive sciences at Yale School of Medicine and clinical research team leader of gynecologic oncology at Yale Cancer Center, emphasizes what this means for his patients. "People with treatment-resistant uterine cancer have very limited options," he says. "That's why it's so important to develop new treatments."
The drug's story begins with a collaboration between Santin's team and pharmaceutical company Immunomedics (now part of Gilead Sciences). They engineered sacituzumab govitecan to use antibodies to bind directly to Trop-2, effectively creating a molecular delivery system that could ferry chemotherapy to cancer cells while minimizing collateral damage. The FDA approved it for late-stage breast cancer in 2023; this trial represents its first major test in uterine cancer.
The treatment did exact a cost. Many patients experienced bone marrow suppression, reduced white blood cell counts, and gastrointestinal problems including diarrhea. Yet Santin stresses that these side effects proved manageable with supportive care and remained significantly less toxic than standard chemotherapy drugs. For patients with no other options, that trade-off may be worth making.
The success of this Phase II trial has cleared a path forward. Santin's team is now planning a Phase III clinical trial—a larger, more rigorous test—to confirm sacituzumab govitecan's effectiveness in treatment-resistant uterine cancer. If those results hold, women facing one of gynecology's most challenging diagnoses may finally have a meaningful next step.