It’s a troubling trend: Cases of uterine cancer are increasing rapidly across the U.S., as is the mortality rate. Further, an unsettling racial component exists, with Black women having a higher likelihood of aggressive disease and death than white women. In fact, Black women are nearly twice as likely to die from uterine cancer — also referred to as endometrial cancer — than any other racial or ethnic group.
This reality has pushed WashU Medicine physicians and researchers at Siteman Cancer Center to carry out groundbreaking research to address this racial disparity and identify new treatments that can benefit all women.
“In the past five years, we’ve witnessed a startling surge in endometrial cancer cases,” noted gynecologic surgeon Dineo Khabele, MD, the Mitchell and Elaine Yanow Professor of Obstetrics & Gynecology and head of the Department of Obstetrics & Gynecology at WashU Medicine. “It’s affecting more women in the U.S. than ever before, and alarmingly at much younger ages.”
Specialized Program of Research Excellence (SPORE) grants are awarded by the National Cancer Institute to leading cancer centers conducting the most cutting-edge translational research in various cancer types. WashU Medicine has been awarded SPORES in blood, endometrial and pancreatic cancer, placing the research institute among a tiny vanguard of universities that have been awarded a trio of SPOREs. Major components of these prestigious grants include innovative research projects with an emphasis on early-stage clinical trials.
WashU Medicine is a longtime leader in the study and treatment of endometrial cancer, first receiving a prestigious National Cancer Institute Specialized Program of Research Excellence (SPORE) grant for endometrial cancer in 2009. A new SPORE grant in 2023 — the only one awarded in the U.S. — is allowing WashU Medicine researchers to investigate what is driving recent increases in endometrial cancer cases and deaths as well as the racial disparities seen in this cancer type.
Collaborating with the University of New Mexico and the University of Oklahoma Health Sciences Center, the three WashU Medicine endometrial SPORE locations — and the diverse patient populations they serve — are providing an opportunity to better address endometrial cancer in patients who have been historically underrepresented in cancer research and clinical trials and are disproportionately affected by endometrial cancer, including Black, American Indian and Hispanic patients.
“We hope our studies will shed light on racial disparities we see in endometrial cancer,” said David G. Mutch, MD, the Ira C. and Judith Gall Professor of Obstetrics & Gynecology and principal investigator of the endometrial cancer SPORE. “We’re reaching out to diverse groups of patients to be sure our participants accurately reflect the individuals who develop this cancer and to be sure any research findings apply to and have the potential to benefit all patients. If we have a better understanding of racial disparities in endometrial cancer, we can take steps to reduce them.”
As part of the endometrial SPORE, one team of WashU Medicine researchers is evaluating investigational drugs that inhibit important molecules called heat shock proteins, which have roles in tumor cell growth and metastasis.
A second team of researchers is testing inhibitors that target an aggressive uterine cancer by blocking a key protein called a receptor tyrosine kinase. And a third is focused on the possibility of early detection and prevention of endometrial cancer through weight-loss strategies.
“The SPORE in endometrial cancer gives patients opportunities to participate in innovative clinical trials that have potential to improve outcomes for those affected by this cancer,” Khabele added. “It also will help build a strong foundation for training early-career investigators, so they will have the support they need to advance work in this important area.”
Beyond the SPORE grant, Matthew A. Powell, MD, the Ira C. and Judith Gall Professor of Obstetrics & Gynecology, recently co-led national studies showing that adding immune checkpoint inhibitors to standard therapy for endometrial cancer improves outcomes for many patients. Checkpoint inhibitors help unleash T cells, giving these vital immune cells a better shot at eradicating a tumor.
The immunotherapies worked particularly well against endometrial tumors with certain genetic characteristics called mismatch repair deficiency and high microsatellite instability. Powell was a co-senior author on two studies showing these results. The findings were published in 2023 in The New England Journal of Medicine and are changing the standard of care for advanced endometrial cancer.
“With these recent advancements in immunotherapy and our ongoing clinical trials through the SPORE,” Mutch said, “we are able to offer more options for our patients now than we ever have, and we will continue working to move the field forward.”
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Published in the Autumn 2024 issue