Accelerating microbiome research in endometrial cancer

Research

Accelerating microbiome research in endometrial cancer

By
Mayo Clinic Staff

January 10, 2023

Marina Walther-Antonio, Ph.D., Departments of Surgery and Obstetrics and Gynecology at Mayo Clinic in Rochester, is a pioneer in studying the role of the microbiome in women’s health. Dr. Walther-Antonio is also Dean of Diversity, Equity and Inclusion in the Mayo Clinic Graduate School of Biomedical Science and an assistant professor in the Mayo Clinic College of Medicine and Science. She’s investigating the possibility that a microbe her team has identified in the vagina and uterus is a contributor to endometrial cancer. Most women don’t have this microbe, Porphyromonas somerae (P. somerae), in their vaginal or uterine microbiome. However, it is present in small amounts in 86% of women who have endometrial cancer.

Little research has been conducted about P. somerae. Several reports show it has been found in chronic bone and tissue infections of people who have diabetes. Dr. Walther-Antonio, a full-time faculty member in the Mayo Clinic Center for Individualized Medicine’s Microbiome Program, and her team are studying how this uncommon microorganism persists in the reproductive tract. They’ve completed three studies that link P. somerae to endometrial cancer.

Dr. Walther Antonio leans against a white wall — Marina Walther-Antonio, Ph.D.

P. somerae produces succinate, which can interfere with normal cellular functioning and accelerate cancer-causing pathways. P. somerae also is stimulated by estrogen exposure — a risk factor for endometrial cancer. One possibility Dr. Walther-Antonio’s team is investigating is that P. somerae invades endometrial cells in the uterus and produces succinate, compounding an individual’s risk.

Dr. Walther-Antonio and her team are the first to make this discovery, published in Frontiers in Microbiology. Now she wants to use this information to predict which women may develop cancer and find a way to intervene and prevent it.

“Our goal is to move the field beyond simple association and correlation and into proof of pathogenic behavior,” says Dr. Walther-Antonio. “This will be a significant leap toward understanding the role of the microbe in the disease and places us one step closer to identifying new therapeutic targets and being able to help patients.”

In addition to therapeutic targets, Dr. Walther-Antonio would like to develop a test for endometrial cancer, using this finding of P. somerae as an early-detection biomarker.

“Most endometrial cancer is detected early because it’s symptomatic, with vaginal bleeding,” she says. “More severe cases, however, don’t manifest that way, so aggressive cases often aren’t detected until later stages of the disease. Black women are more likely to have more aggressive cases as well as symptomatic fibroids, so they and their physicians may overlook bleeding as a concern.”

Dr. Walther-Antonio is planning work with Emory University and Johns Hopkins University to gain access to larger numbers of Black women for her research. She’s committed to addressing what she calls a serious public health problem with a disproportionate impact on minority populations.

“Endometrial cancer kills twice as many Black women as white women, making it the leading cancer-related health disparity in women in the U.S. The current test for endometrial cancer is an endometrial biopsy, which can be painful and expensive. We envision developing a vaginal swab test for endometrial cancer biomarkers that a woman could take at home and send to a laboratory for PCR testing. That’s the ultimate translation of our research — providing those at greatest risk with an easy-to-use predictive test so we can intervene and treat them with therapeutic agents to stop cancer in its tracks.”

This article was originally published in Alumni Magazine, 2022, issue 3.