“One of the biggest issues with improving delivery of chemotherapy to solid tumors is that only about half of the blood vessels are functional and mature enough to deliver the drugs,” she says. “We’re working on ways to improve the function of the blood vessels so we can get chemotherapy to the places that need it most – the tumors.”
Her lab’s work in mouse models is based on the premise that an increase in blood flow encourages blood vessels to grow and mature, and the best way to reliably increase blood flow is through exercise. Schadler and her colleagues have shown that mice with pancreatic cancer, melanoma and Ewing’s sarcoma have better outcomes and better responses to low dose chemotherapy when on an exercise regimen.
“Moderate exercise five days a week was shown to be effective,” she says. “We’re still trying to determine whether it’s frequency or intensity that is most important, but our preclinical studies intentionally use very moderate exercise.”
That’s good news for our patients, who often experience fatigue and other side effects that may make it difficult for them to participate in strenuous activities.
Studying exercise’s impact on pancreatic cancer treatment
Schadler met some of her clinical colleagues with similar interests when presenting a poster at a conference. Surgeon Matthew H.G. Katz, M.D., and rehabilitation specialist An Ngo-Huang, D.O., had just finished a clinical trial on exercise in pancreatic cancer patients and its effects on surgical outcomes. Schadler looked at some patient samples from their trial and saw the same pattern of vascular remodeling in their patients and her mice.
They’ve since launched a randomized clinical trial of exercise versus usual care for patients with pancreatic cancer on chemotherapy and/or chemoradiation treatment. Ngo-Huang oversees the exercise portion and may assess the patients in clinic if they have a physical condition or injury that makes it difficult for them to complete the prescribed regimen.
“We’ve designed the exercise regimen so that patients can do this anywhere,” she says. “If they’re unable to go to the gym or they live far from MD Anderson, they still can participate. And most importantly, they can get the proven benefits of exercise, such as reduced fatigue.”
Nathan Parker, Ph.D., a postdoctoral fellow in Behavioral Science, follows up with the patients throughout the study. He checks to make sure they’re sticking with the program, provides strategies to motivate them to exercise and looks out for any issues they may be having.
“We’re really pleased with the levels of motivation we see in our clinical trial patients,” he notes. “We explain that it’s really important to stay fit during treatment, and they appreciate having exercise as a component of treatment that’s within their control.”
Making exercise fun
Schadler also is working with clinical partners to study the effects of exercise on blood vessels in pediatric sarcoma patients. Valerae O. Lewis, M.D., and her physical therapy team have been working closely with Schadler on a study to see if exercise can be used to improve delivery and effectiveness of chemotherapy in treating young patients, especially those with osteosarcoma and Ewing’s sarcoma, the most common malignant bone tumors diagnosed in children and young adults.
Schadler’s trial has one group of these patients working three times a week with a physical therapist, one group with a prescribed at-home exercise regimen and one group receiving general healthy living advice.
Schadler and her partners are hoping to find markers in the blood that correlate to the vascular changes and can be used in future clinical trials to measure whether a patient has exercised enough.
“We want to see how the endothelial cells in the vessels are affected on a molecular level to induce this maturation and improved function,” she says. “What targets do we need to activate to make the vessels grow? After we identify those, we can work on finding a way to give every patient a personalized prescription for the amount of exercise needed for the best outcome.”
She’s also working with all pediatrics patients to increase their culture of activity. To help, MD Anderson’s Energy Balance and Integrative Medicine team brings in collegiate and professional athletes to play games and exercise with the kids, with the goal of making exercise fun. “MD Anderson has a lot of support for exercise and nutrition research, and we’re really moving forward,” Schadler says.
“This is the only place where basic scientists, exercise physiologists, rehabilitation specialists and cancer physicians all can work together to make a difference for patients.”
A longer version of this story originally appeared in Messenger, MD Anderson’s quarterly publication for employees, volunteers, retirees and their families.