Title:Ruesch Center Targets Gastrointestinal Cancers

The Evolution of the Ruesch Center

According to the American Cancer Society, the collective cancers of the GI tract have the highest incidence and are the second leading cause of cancer deaths in the United States. These include cancers of the colon, rectum, esophagus, stomach, liver, pancreas, and bile ducts/gallbladder. Although GI cancers usually affect individuals later in life, since 1995, there has been a 22 percent increase in the incidence of GI cancers diagnosed before age 50.

Despite this trend, funding for GI cancer research has traditionally been scarce. Just a decade ago, breast cancer research garnered ten times more money than all other cancers combined. The picture has improved, but the funding gap still exists and may be attributable in part to the general public’s lack of awareness of GI cancers.

The Ruesch Center aims to change that. Together with Marshall and the Center’s care team, Jeanne Ruesch has steadfastly infused her vision of hands-on advocacy and research to jumpstart studies on better treatments and care, to improve the quality of life for patients with GI cancers.

Leveraging Cancer Biology

Marshall notes that out of the gate, he and Jeanne Ruesch aimed high. They purposefully chose to use the word “Cure” in the name of the Center. They stay laser-focused on finding better treatments for the patients who fill the clinics, the majority of whom have metastatic cancers.

“We knew we needed to reach for the stars,” says Ruesch. “We both believe that curing these patients will be possible someday.”

When reflecting on the last decade since the Center’s inception, Marshall underscores the growing impact of precision and personalized medicine in treatment decision making. The first step in doing that was to divide GI cancers into different sub-groups, to identify which patients should get which therapies.

“It seems so obvious now,” he says. “But it took a while to recognize that we’re dealing with hundreds of diseases, and they all can’t be treated the same way.”

Indeed, each person’s cancer has a unique “signature” that can be revealed through a test called tumor or molecular profiling. By sequencing a cancer’s genes, mutations may be identified that can act as targets for various therapies, often administered to the patient as part of a clinical trial.
Immunotherapy is another promising strategy for fighting these aggressive cancers. Elegant in its simplicity, this approach relies on rallying cells in the body to recognize and attack the cancer.

“There was a time when we thought that stimulating the immune system would never work,” Marshall says. “We now know that cutting the brakes off of the immune system so that it can destroy cancer cells has dramatically influenced cancer care.”

Marshall believes that unlocking the secrets of GI cancers, and ultimately curing them, may lie in the crosstalk between the immune system and the microbiome—the trillions of bacteria, fungi, and viruses that live within and on our bodies.

Several intriguing findings support this theory. For example, bacterial DNA has been identified in colorectal liver metastases, leading to questions about the causative role that bacteria may play and how they may help cancer cells evade detection by the immune system.

Another recent observation in small studies is that stool transplants may improve response to immunotherapy. By using stool to transfer the microbiome from a healthy individual into the colon of a cancer patient, cancer cells become vulnerable to reinvigorated immune cells.

Finally, research is ongoing to figure out why left- versus right-sided cancers often present and behave differently. The bacterial habitat of the colon could explain why location matters when it comes to treatment and prognosis.

Mud Pies and Green Tea

What can these revelations about treatment tell us about the cause of GI cancers, and why more young people are getting diagnosed? Marshall points out that changes in our lifestyle habits over the years may affect the microbiome.

In response, we need to train our microbiomes better. As Marshall is fond of saying, “eat more dirt!” (Or make mud pies, like he did when he was a kid.)

“Exposure to microbes in our everyday environment might teach our immune systems to fend off disease,” says Marshall. However, in the current COVID-19 climate, he acknowledges that giving up disinfecting wipes and handwashing rituals is not likely to happen. He speculates that these protective behaviors today may not bode well for gut health in the long term. Fortunately, research is illuminating other ways that we can reduce the risk of GI cancers.

For example, Georgetown researchers are studying a com- pound that occurs naturally in green tea and may bolster liver health. Patients with cirrhosis are good candidates for prevention, given that they have a very high risk of developing liver cancer. A pilot consortium study is evaluating what the effects are of the green tea extract in such patients. And a large multisite NIH study is assessing whether a specific biomarker in the liver can be used to predict the risk of liver cancer development or recurrence.

Aiwu Ruth He, MD, PhD, associate professor at Georgetown Lombardi Comprehensive Cancer Center and the scientific lead for liver and biliary cancers within the Ruesch Center, is a principal investigator on these studies. Collaborators include Fung-Lung Chung, PhD, professor of oncology at Georgetown, who studies how DNA damages generated from activities in a person’s own body result in cancer development. Chung provides scientific support for the NIH study. In addition, Coleman Smith, MD, a liver specialist at MedStar Georgetown University Hospital, helps to identify patients for the research.

“The goal of these studies is to identify people with an increased risk of developing liver cancer, then treat them with green tea to lower their risk,” says He. “We would much rather prevent the cancer than treat it,” she adds.

An Alliance of Advocates

Marshall’s vision, which he projects on and beyond the Georgetown hilltop, embraces a culture of advocacy to move the field forward.
In 2015, the Ruesch Center founded the GI Cancers Alliance. The coalition, whose mission is to bring awareness and education to the public, unites forty advocacy groups with academic centers and industry leaders to accomplish this goal.

“I don’t think it’s an overstatement to say that the Ruesch Center catalyzed this movement,” Marshall says, noting that this tour de force has contributed to the Center’s continuous investment in scientific study. In fact, all Ruesch Center philanthropy is earmarked for research. This commitment has unified leading researchers and clinicians in multidisciplinary, transformative collaborations around the globe.

Investing in Bold Ideas and Planting the Seeds

Private philanthropy cannot replace government funding in terms of dollar amounts and the scope of supported research. But one thing that Ruesch, Marshall, and He all recognize is that the Ruesch Center’s commitment to funding early-stage basic science research goes one step further. It empowers scientists to test their out-of-the-box hypotheses that might be deemed too “risky” by extramural agencies.

“This kind of seed funding is the honey that drew the bees,” says Marshall. And those bees turned out to be a team of innovative clinician-scientists such as He and Chung.

The human trial examining green tea extract for liver cancer prevention came about after the Ruesch Center funded a pilot, which sought to determine if intriguing animal model data generated in Chung’s lab could be replicated in human tissues in the laboratory.

These kinds of preliminary data have driven He and her colleagues to shoot for the moon. Indeed, she is the site principal investigator for an NCI Moonshot project assessing the role of biomarkers in predicting the response of liver cancer patients to immunotherapy.

“We were selected as one of the sites based on a pilot study funded by the Ruesch Center,” He says. “Other considerations were our active contribution to many clinical trials that are evaluating immune therapies in liver cancer, and the comprehensive care of these patients by our robust multidisciplinary team.”

She adds that unlike extramural reviews, the internal review process within the Ruesch Center is dynamic, interactive, and undertaken with a collaborative spirit. For He, the review process itself led to acquiring new collaborators.

“I didn’t just get funding,” she says. “I gained a community.” Bringing this community of innovative scientists together is precisely the mission of the Ruesch Center.

“The best philanthropy makes room for scientists to make mistakes and then learn from them,” says Jeanne Ruesch. From there, she adds, “We expect and respect the ability of our funded researchers to leverage their preliminary data to obtain the big, often federally funded grants.”

Cancer Gets Personal

There is no doubt that the evolving science ignites passion in Marshall. But the cures ultimately take place at the bedside, not the laboratory bench. Tending to patients is something he always prioritized—now more than ever.

To be sure, each of Marshall’s patients has left an indelible impression on him. But when his wife Liza was diagnosed with an aggressive triple-negative breast cancer in 2006, his perspective changed completely. Through her surgery, chemo, and radiation, he tamped down his doctor impulses to focus on being present as a caregiver and husband first and foremost. Both John and Liza Marshall were humbled by the level of care and attention that Liza and their family received.

Liza is now cancer-free, and the doctor pays this gift forward through his leadership and patient care at the Ruesch Center.

“We’re delivering turnkey services to patients and their families, in a setting that combines cutting edge-treatment merged with care and compassion,” Marshall says.

These are the qualities Ruesch saw in him as her husband’s physician, and form the legacy of the Center for future patients and their families.

Beth N Peshkin, MS, CGC, is a professor of oncology and director of genetic counseling at Georgetown Lombardi Comprehensive Cancer Center. This year she celebrates 25 years at Georgetown.