Donors through the Foundation were pivotal to jumpstarting Dr. David Mutch’s pioneering research on endometrial cancer. Those early investments continue to accelerate discoveries, better treatments, and expanded research avenues—including the Route 66 Endometrial Cancer SPORE.
In the early 1990s, most gynecologic oncology researchers around the country were focused on studying ovarian cancer. That fact struck David Mutch, MD, as a young researcher and OB/GYN clinician at Washington University School of Medicine, considering endometrial cancer was a more common disease. So he joined with scientist Paul Goodfellow, PhD, to blaze a new trail in endometrial cancer research. Thirty years later, their pioneering efforts have led to research projects and breakthroughs in treatments that span the country.
While progress has been made, more research is needed. Endometrial cancer incidence and death rates have inched up in the past decade, with a disproportionate impact on women of color.
The reasons for the increase in cancer of the lining of the uterus aren’t yet fully understood. But Dr. Mutch, who is now professor, vice chair of OB/GYN at WashU Medicine, is determined to turn the tide of the deadly disease in collaboration with a group of fellow researchers.
Over nearly 40 years at WashU Medicine and Barnes-Jewish Hospital, Dr. Mutch has become a nationally renowned clinical expert in the field of gynecologic oncology and has played a vital role in establishing clinical practice guidelines used across the country. Endometrial cancer research—both understudied and underfunded—has been an integral part of Dr. Mutch's career.
Now, Dr. Mutch and an interdisciplinary team of scientists are embarking on a five-year, multi-center collaboration between WashU Medicine, the University of Oklahoma Health Sciences, and the University of New Mexico, which are all located along historic Route 66, crossing the Midwest and Southwest. The Route 66 Endometrial Cancer Specialized Program of Research Excellence (SPORE) provides $11.6 million to change the trajectory for patients with or who are at risk for endometrial cancer through the development of new treatment and prevention strategies.
Laying the Foundation for Progress
Dr. Mutch’s research projects over the years have flourished with support from donors to The Foundation for Barnes-Jewish Hospital. Those donors include Michael Staenberg, who established the Staenberg Family Gynecological Cancer Research Fund at the Foundation in 2003 in honor of his mother.
“Dr. Mutch is a hero in my book,” Michael says. “He represents everything Siteman Cancer Center is about. He genuinely cares about making a positive difference in people’s lives.”
Early donor support has multiplied into exponential benefits, including two prestigious SPORE grants from the National Cancer Institute (NCI). SPORE grants provide an umbrella of research funding for research projects along with the administrative, statistical, and pathology services they need to succeed. They also include a package of funding to enhance the careers of junior investigators and develop new experimental approaches. 
In 2009, Dr. Mutch and Dr. Goodfellow received the first-ever SPORE dedicated to endometrial cancer from the NCI. It came on the heels of landmark discoveries identifying genetic abnormalities that played a role in developing endometrial cancer that put the team in the national spotlight.
Dr. Mutch credits the support they received from the Staenberg Family Gynecological Cancer Research Fund and other donor funds that laid the foundation needed to receive the first SPORE.
The NCI’s first three-year grant of $1.7 million funded research into improved detection and treatment of endometrial cancer. It also sparked the growth of a tissue bank.
Recognizing a need, Dr. Mutch led an initiative in 1992 to establish the Gynecologic Oncology Tissue Bank at WashU Medicine to support gynecological oncology research. Now led by Mary Mullen, MD, a WashU Medicine gynecologic oncology specialist, the tissue bank has achieved national prominence and accumulated specimens from over 3,000 endometrial cancer and 1,500 ovarian cancer patients.
“The tissue bank helped us better understand the molecular features of endometrial cancer that has led to more targeted therapy,” Dr. Mutch says. “In addition, the team’s research from the first SPORE led to patient care changes in place today. We now better understand the significance of mismatch repair in this disease, and we’re able to foster investigators in this area. For example, Dr. Matthew Powell, a WashU Medicine gynecologic oncology surgeon, became the chair of the endometrial committee of the NRG, an international cancer research collaboration. His leadership has led two clinical trials that have changed the way we treat endometrial cancer using immunotherapy.”
The Staenberg Family Gynecological Cancer Research Fund continues to fund tissue collection through the bank. Currently, a research team (separate from the SPORE team) is evaluating tissue to identify genes responsible for inherited endometrial and ovarian cancer and to identify the specific mutations responsible for cancer growth. The team is also analyzing data to determine risk factors that lead to endometrial and ovarian cancers.
Donor support also has allowed the research team to expand. “We’ve established strong leadership in the field,” Dr. Mutch says. “We have grown from two scientists to a robust, multidisciplinary program that includes fellowship training, radiation oncology, genetic counseling, and psychology.”
Investigating Disparities
The Route 66 Endometrial Cancer SPORE grant was built on the shoulders of the first endometrial cancer SPORE. Philanthropy also played a major role.
“Generous philanthropy has been an essential building block for life- changing endometrial cancer research progress,” says Dr. Mutch, the SPORE’s principal investigator. “SPOREs encourage interdisciplinary research to move laboratory studies to patient care more quickly.”
A unique aspect of the Route 66 SPORE is that it focuses on addressing health disparities associated with endometrial cancer in Black, Native American, and Latino patients—who have been historically underrepresented in cancer research and are disproportionately affected by endometrial cancer.
“What excites me about this new SPORE is that for the first time, we’re deeply investigating the disparities within the treatment and incidence of endometrial cancer,” Dr. Mutch says. “This aligns with the incredible focus that Dr. Tim Eberlein has made on health equity as the leader of Siteman.” Tim Eberlein, MD, is the director of Siteman Cancer Center at Barnes- Jewish Hospital and Washington University School of Medicine.
The Route 66 SPORE is the only one of its kind to include a formal health equity advisory board, Dr. Mutch points out. The Endometrial Cancer Equity Group, which includes members of the research team, clinicians, nurses, and public health professionals, is working to promote the inclusion of underrepresented cancer patients in research and clinical trials through national collaboration.
“Having this SPORE at Siteman gives patients access to clinical trials and potential breakthrough treatments right here in St. Louis,” Dr. Mutch says. “And we’re able to enroll underserved women in this region in our clinical trials.”
A SPORE of Many Strengths
The Route 66 SPORE also includes a project focused on early detection and prevention through weight loss strategies, as obesity is a major risk factor for endometrial cancer. Andrea Hagemann, MD, MSCI, WashU Medicine gynecologic oncology surgeon, is the principal investigator of SPORE Project 3. Her two new clinical trials will test whether lifestyle modification and weight loss can reverse early cancer, treat pre-cancer, and preserve the uterus in young, premenopausal women who desire future fertility. These trials are now enrolling at WashU Medicine.
Dr. Hagemann co-leads Project 3 with Kim Leslie, MD, a renowned endometrial cancer researcher at the University of New Mexico.
In two other projects, scientists are testing new treatment targets and drugs. In addition, scientists hope to identify biomarkers that can predict the development of endometrial cancers, among other aims.
Dr. Mutch says the SPORE at WashU Medicine offers the research team access to lab resources not found in many other places.
“One of the unique strengths of our program is that we can monitor the metabolic response patients are having during treatment,” he says. “WashU Medicine has one of the most leading-edge metabolomic cores in the world, led by Dr. Gary Patti and Dr. Ian Hagemann, that gives us the ability to look at the effect of drugs on the cancer cells moment to moment. This insight lets us know how the drug is working in real time.”
Gary Patti, PhD, who is a leader in cancer metabolomics, serves as the senior director of the Center for Mass Spectrometry and Metabolic Tracing, as well as director of the Clinical Research Core in Medicine at WashU Medicine. His lab is leveraging innovative metabolomics approaches to determine how a patient’s diet can influence the development and progression of certain types of cancer.
“We have pioneered metabolomics technologies to track where nutrients go in tumors,” Dr. Patti says. This pathway is important because tumors use fuels, such as sugar and fat, in ways that are distinct from healthy tissues. The researchers hope that, by mapping out those differences in patients with endometrial cancer, they will identify markers to guide patient therapy and ultimately find new anticancer targets for treatment.
“No one has ever done these kinds of experiments in endometrial cancer before,” Dr. Patti explains. “It was the visionary insight of Dr. Mutch to bring together these key strengths at WashU Medicine in endometrial cancer and metabolomics. I don’t know of any other place in the world with the capabilities and expertise to execute this type of study.”
Ian Hagemann, MD, PhD, is a WashU Medicine gynecologic pathologist with clinical and research interests in endometrial cancer. He co-leads the Biospecimen, Metabolomics, and Pathology Core of the SPORE with Dr. Patti and Mark Watson, MD, PhD.
The core provides access to tissue- related services, leveraging existing resources at WashU Medicine.
“This core is a resource available across all of the Route 66 SPORE partner sites to provide high-quality pathology expertise, metabolomics expertise, and sample management to the biological specimens collected during the SPORE research projects and clinical trials,” explains Veronica Davé, PhD, research project manager and SPORE administrator. “The SPORE provides key interdisciplinary infrastructure support like this core to the projects, which enables us to do strong team science.”
The Foundation for Barnes-Jewish Hospital continues to play a key role in supporting this team effort.
“The interdisciplinary collaboration in the Route 66 SPORE is a model example of how early investments from donors are catalysts for so much more growth in the long-term,” says Mary Hendricks, executive director of philanthropy at the Foundation. “We’re grateful for the compassionate, visionary gift from the Staenberg family more than 20 years ago that continues to spark more research and better patient care every day.”
Mentoring Future Lifesavers
A dedicated mentor, Dr. Mutch plays an instrumental role in ensuring highly skilled young investigators are well trained and prepared to lead cancer research projects into the future. He has mentored hundreds of residents, fellows, and junior faculty throughout his career. Of the more than 50 fellows he has mentored, nearly half have gone on to assume leadership roles in various academic gynecologic oncology programs throughout the country.
To continue that successful legacy, the Route 66 SPORE includes a Career Enhancement Program to drive innovation in the field by mentoring early-stage and advanced physician- scientists interested in endometrial cancer research.
Dr. Mutch says Dineo Khabele, MD, head of the WashU Medicine department of obstetrics and gynecology, has been critical in driving the SPORE forward. 
“The SPORE grant fuels the vision Dr. Khabele established to build a strong foundation of support and training for early-career investigators to bring the research work and knowledge into the future. Dr. Eberlein also has been a tireless supporter of our work, supporting this with faculty and resources.”
He continues: “The beauty of the SPORE is that it gives infrastructure support to Siteman and endometrial cancer research and will fund projects by young investigators. The SPORE also draws new people into research in endometrial cancer, which is a majorly underfunded disease for research compared to breast or prostate cancers. By developing new ideas, investigators, and collaborations, we will expand the breadth and depth of research aimed at treating or preventing endometrial cancer.”
The progress seen over the past 15 years was built on the momentum from the first SPORE, Dr. Mutch adds.
“Receiving the second SPORE is a result of persistent and ongoing research. And a big reason we’ve been able to do that is because of donor generosity through the Foundation. This is a huge team effort by the University and department leadership, as well as faculty and staff. It definitely takes a village.”
Seeing It Through
After decades of pioneering research, Dr. Mutch continues his quest. Although the South Dakota native enjoys leisure time on his Missouri ranch surrounded by cattle and nature, most days you’ll still find him in his white lab coat immersed in discussions of cells and tissue with other scientists. He’s driven to continue his research as he mentors and trains the next generation of investigators.
“It gets in your blood, and I want to see it through,” he says. “It’s exciting to see the progress we’ve made over 30 years—and there is much more to come. The ongoing support from the Staenberg Family Gynecological Cancer Research Fund gives us critical flexible funding to maintain projects into the future and expand their scope beyond what we are funded to do in the SPORE. This allows us to grow projects in new directions or address unanticipated areas of need.”
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Written by Joyce Romine
Photography by Alex Kendall