There have been increasing rates of early-onset uterine cancer, but a scientific member of the Molecular Therapeutics Research Program at the Barbara Ann Karmanos Cancer Institute has been awarded a V Foundation for Cancer Research grant in the hopes of helping to change this.
“Endometrial (uterine) cancer is diagnosed in about 70,000 patients per year in the U.S.,” said Michael Wilson, Ph.D., the grant recipient. “Of those, about 10% are early-onset cases, about 7,000 new cases per year. Survival of endometrial cancer is generally good at lower stages, and this is also true for patients with early-onset disease. Still, the primary treatment is hysterectomy, which may not be ideal for younger patients. For advanced cases of endometrial cancer, survival is as low as 20%.”
Dr. Wilson has been given a three-year, $600,000 V Scholar Program grant from the V Foundation for Cancer Research, which begins Oct. 1, 2025. This award benefits Dr. Wilson’s team’s research in epigenetic mechanisms and therapeutic targets in early-onset endometrial cancer. A patient under 50 diagnosed with endometrial cancer would be considered having early-onset disease.
“We are trying to determine what makes the tumors of the patients with early-onset unique and how we can use that information to try and guide new therapeutic development for specific treatments targeted at early onset,” Wilson said, who is also an assistant professor in the Department of Oncology at Wayne State University.
“The work will focus on a gene we identified through the literature and our own studies, called KMT2D, which is mutated at a much higher rate in the tumors from patients with early-onset uterine cancer,” he explained. “We are investigating the gene mutation's role in cancer development.”
Dr. Wilson and his team did preliminary work, developing genetically generated pre-clinical models of endometrial cancer, which also had this mutation in KMT2D.
“We found that the models with this additional mutation with KMT2D compared to the original model of endometrial dysfunction were far more likely to develop cancer than the original model,” he described. “The model with KMT2D mutation had a cancer rate of 72% compared to 20% in the original model. The pre-clinical models are also dying more quickly and developing more aggressive tumors. This indicates that this gene is a potent tumor suppressor gene. We will continue studying this model, which we believe to be a compelling model of early-onset endometrial cancer.”
They identified unique genetic signatures in those tumors, which led them to believe that a specific type of therapy, the CDK 4/6 inhibitor, may be relevant to the treatment of uterine tumors with KMT2D mutation.
“The grant aims to characterize our disease models further and try to understand how the KMT2D mutation promotes cancer,” Dr. Wilson said. “Our second aim is to test whether CDK 4/6 inhibitors would be effective therapies in this tumor type using the models we developed.”