Making the Connection Between Obesity and Cancer

Obesity is one of the most significant and preventable risk factors for cancers. Linked to 13 cancer types, it may contribute to poorer outcomes after diagnosis. Excess body fat drives hormonal, inflammatory and metabolic changes that can fuel tumor growth. Nearly 70% of people living in The University of Kansas Cancer Center’s catchment area have obesity or are overweight, which is why understanding the cancer-obesity connection is a strategic priority. 

To expand obesity research opportunities, in 2025, the cancer center hosted its first Obesity, Metabolism and Cancer Conference, bringing together more than 75 researchers, clinicians and community partners to explore how metabolic health shapes cancer risk, treatment response and survivorship. 

Across the cancer center, researchers are examining obesity from many angles, from molecular pathways that influence tumor growth to designing community-based prevention programs. The highlights below provide a glimpse of these efforts, demonstrating how research across the continuum is advancing our understanding of the cancer-obesity connection. 

Repurposing a Weight Loss Drug 

Can substantial weight loss aided by tirzepatide, a dual GLP-1 and GIP receptor agonist, reduce breast cancer risk in women with obesity? That is the question behind a first-of-its-kind pilot study led by breast cancer prevention researcher Carol Fabian, MD, and obesity expert Cathleen Beaver, MD.

The six-month study, launched in 2024, enrolled 25 women with obesity and additional risk factors for breast cancer development. Participants received weekly tirzepatide injections, a drug originally developed for type 2 diabetes and now approved for weight loss. 

Studies show that losing ≥10% of body weight in women with obesity improves biomarkers linked to breast cancer risk, and sustained losses of 10–20% are associated with lower incidence. Yet, achieving and maintaining that level of weight loss without bariatric surgery remains a challenge. According to Drs. Beaver and Fabian, tirzepatide may offer a breakthrough, as studies in the general population who are obese showed 10% or greater relative weight loss at six months and up to 20% at 12 months. 

“More than two-thirds of the participants have completed the study, and only one participant withdrew prior to the six-month mark,” says Dr. Fabian. “With a median 15% relative weight loss at six months, we are seeing encouraging early signs in blood, breast imaging and breast tissue.” 

While weight loss improves system markers like insulin resistance and inflammation, the team is investigating whether these drugs also alter breast tissue itself, potentially lowering cancer risk at its source. Early data, presented at the San Antonio Breast Cancer Symposium and RISE UP for Breast Cancer conference, suggest that in some participants, receptors are present on cells in the breast epithelium, the layer of cells where most breast cancers begin. 

The study includes researchers from The University of Kansas Cancer Center and is funded by a pilot grant from the cancer center, with support from the Breast Cancer Research Foundation, Jedel Family Foundation and Morris Family Foundation. 

“This work will provide the data we need to conduct a larger trial and potentially give women at high risk for breast cancer a new way to protect themselves through sustained weight loss,” says Dr. Beaver. 

Supporting Rural Health 

Maintaining a healthy lifestyle can be challenging for rural families, making obesity more common than in urban areas. Limited access to grocery stores, exercise spaces and healthcare services all play a role. The iAmHealthy Parents First study, co-led by Christie Befort, PhD, associate director for Cancer Prevention and Control at The University of Kansas Cancer Center, and Ann Davis, PhD, MPH, professor of Pediatrics, is designed to meet rural families where they are, with free, evidence-based support delivered entirely online. 

The goal is to test whether offering a parent-only program before a family-based approach leads to better outcomes for children and caregivers. 

“It’s been a game-changer,” says Mandy Fincham, a rural Kansas mom. Retired school nurse Chris Tuck agrees, calling it a program that empowers parents to be “part of the solution.” 
In the first three months, parents join either a virtual group-coaching program or a self-guided learning track. All participants then move into a six-month family-based program with online fitness sessions, nutrition education and health coach support. Families receive tools like fitness trackers and smart scales and participate in check-ins and surveys. 

“This study gives rural families access to health education and support that might otherwise be out of reach,” says Dr. Befort. “By starting with parents, we are creating a stronger foundation for the whole family.” 

Another effort called the Healthy Living campaign, developed by the cancer center communications and Community Outreach and Engagement teams, uses videos, social media and online materials to raise awareness about the link between obesity, poor diet, inactivity and cancer risk. 

Decoding Tumor Biology 

Using advanced mouse models and human cell lines, Jennifer Davis, PhD, assistant professor of Cancer Biology, and her team study how diet-induced obesity and metabolic dysfunction like high blood sugar and insulin resistance affect tumor growth and spread. 

“One strength of our mouse model is that the animals start out as healthy,” says Dr. Davis. “We can induce obesity through diet and then watch how that affects tumor formation and spread.” 

One study compares a Mediterranean-style diet, which is rich in plant-based fats and fiber, to the standard American diet, which is characterized by refined grains, added sugars and low fiber, to see how different diets influence tumor development. Another researcher is exploring how obesity interacts with a common cancer-driving mutation in the KRAS gene to influence metastasis, or how the cancer spreads. 

“We are asking: Does metabolic dysfunction, such as obesity, increase the chance that a tumor will spread? And does it work together with genetic mutations to make things worse?” Dr. Davis explains. 

Dr. Davis is also looking at data from a large National Cancer Institute trial examining how long-term obesity and type 2 diabetes relate to specific cancers. Her earlier work showed that weight history before diagnosis, not just at diagnosis, can predict colorectal cancer survival. 

Restoring Mitochondrial Health to Reduce Cancer Risk 

Kristy Brown, PhD, co-leader of the cancer center’s Cancer Prevention and Control research program, has uncovered how excess body fat disrupts key hormonal and metabolic pathways, especially the regulation of aromatase, an enzyme that fuels estrogen production in breast tissue. Her work also identified ghrelin, an appetite-regulating hormone, as a natural inhibitor of aromatase, opening the door to a novel class of hormone-targeting therapies. 

Now, with support from a V Foundation for Cancer Research grant, Dr. Brown’s lab is focusing on mitochondria, the tiny powerhouses inside cells. Obesity appears to impair mitochondrial function in breast tissue, leading to DNA damage that may drive tumor development, especially in women with BRCA1 mutations. 

Using breast tissue from high-risk women and BRCA1 mouse models, the team is testing whether lifestyle changes such as exercise and weight loss can restore mitochondrial health and reduce cancer risk. 

Disrupting Cancer’s Energy Supply 

Pancreatic cancer is notoriously hard to treat, partly because its cancer cells are highly adaptable. Michael VanSaun, PhD, associate professor of Cancer Biology, is studying how obesity-driven tumors fuel themselves, and how disrupting their energy supply might slow or stop their growth. 

Cancer cells switch between two major energy sources: mitochondrial respiration (aerobic) and glycolysis (anaerobic). Dr. VanSaun’s lab discovered a protein called SHP2 that is essential for maintaining mitochondrial function in pancreatic cancer. Blocking the protein forces cells to rely on glycolysis, but that alone isn’t enough to kill them. 

“Combining SHP2 inhibition with either KRAS inhibitors or a ketogenic diet, which limits glucose, may ‘starve’ the cancer,” explains Dr. VanSaun. “Early studies show this dual targeting significantly slows tumor growth in mice.” 

In another effort, Dr. VanSaun found that cancer cells secrete signals prompting nearby fat cells to release lipids, which tumors use for energy. His team is working to block these signals or “burn” the fat before the tumor can use it, by activating cold-induced thermogenesis, a process where brown fat generates body heat. Initial results show this strategy also reduces obesity-related inflammation, a known cancer driver.