UMMC scientists take new approaches to tackling Mississippi’s cancer burden

UMMC scientists take new approaches to tackling Mississippi's cancer burden

UMMC scientists are working together to find new ways to improve cancer outcomes for Mississippians.

As the University of Mississippi Medical Center prepares to break ground on a new home for its Cancer Center and Research Institute, or CCRI, scientists are exploring new ways to improve cancer outcomes for Mississippians - from investigating how stress and living conditions affect tumors to uncovering pancreatic cancer's earliest clues and developing more precise ways to deliver chemotherapy.

Inside UMMC laboratories, researchers are working to rewrite Mississippi's cancer story, offering the promise of a different ending - and a new beginning - for patients, families and health care providers.

Their work is driven by intriguing questions: Can a person's environment and life experiences influence how cancer develops and spreads? Can researchers detect pancreatic cancer sooner or deliver treatments more precisely to the cells that need them?

The work takes on added significance as UMMC prepares to break ground Oct. 22 on a new home for CCRI, which is also pursuing designation by the National Cancer Institute. The prestigious recognition is awarded to cancer centers that meet rigorous national standards for scientific research, leadership and collaboration, as well as their ability to turn discoveries into advances in cancer prevention, detection and treatment.

While UMMC's research spans several areas, scientists are united by a central question: Why do some cancers become more aggressive than others, and can understanding those differences lead to better ways to prevent, detect and treat the disease?

Stress, obesity and breast cancer

For Dr. Seema Singh, professor of cell and molecular biology, finding answers begins with understanding why two women diagnosed with breast cancer may have vastly different experiences.

Dr. Seema Singh, professor of cell and molecular biology, is exploring new ways to

Their tumors may behave differently, interact with the body's immune system in different ways and respond differently to treatment.

Singh, also the CCRI associate director of education and training and program director of the Cancer Biology and Therapeutics Graduate Program, is studying how obesity, chronic stress and inflammation may influence the behavior of breast tumors.

"A tumor does not grow in isolation," she said. "It is constantly receiving signals from the body around it. Conditions such as obesity, chronic stress, and inflammation can change hormones, metabolic signals and inflammatory mediators in the circulation. Those signals can reach the tumor and alter how cancer cells and surrounding immune cells behave."

Her research has identified leptin, a hormone associated with obesity, as a possible link between obesity and breast cancer. She is also investigating how cortisol, a hormone released in response to stress, may affect immune cells and the environment surrounding a tumor.

Researchers want to understand whether these signals make certain cancers more aggressive or harder to treat.

The findings could be especially important for understanding triple-negative breast cancer, an aggressive form of the disease with fewer treatment options than some other breast cancers. They want to know why certain molecular subtypes such as this form of cancer occur more frequently or at younger ages in some populations.

Ultimately, Singh hopes to identify biological clues that could help doctors recognize women at greater risk of aggressive disease and determine which treatments might work best.

When life experiences leave a biological mark

Dr. Jasmine Miller-Kleinhenz is taking a closer look at that connection, examining how neighborhood conditions and life experiences may leave lasting changes in the body - including changes linked to breast cancer.

Miller-Kleinhenz

Miller-Kleinhenz, assistant professor in the Department of Population Health Science at UMMC's John D. Bower School of Population Health, studies social epigenomics. In everyday terms, the field explores how social experiences and environmental conditions can influence whether certain genes are turned on or off without changing a person's underlying DNA.

"We cannot separate our bodies from our environment," Miller-Kleinhenz said. "Our bodies are constantly responding to what we experience and are exposed to in an effort to keep us healthy."

Consider the body's reaction to danger. The heart beats faster, energy rises and the senses sharpen. This fight-or-flight response helps people react to an immediate threat.

But what happens when stress does not go away?

Living in an unsafe neighborhood or lacking social support, for example, can create ongoing stress that keeps the body's defenses activated. Over time, that prolonged response may contribute to biological changes associated with cancer.

Miller-Kleinhenz's research has found that women living in economically disadvantaged neighborhoods or communities affected by longstanding social and economic inequities have changes in how genes are regulated within their breast tumors. Those changes are associated with more aggressive cancer and a greater risk of dying from the disease.

Larger studies are needed to confirm the findings and identify which environmental exposures and genes are involved.

Prostate cancer: Looking beyond genetics

The connection between life experiences and cancer is also central to research by Dr. Ajay Singh, who is exploring why prostate cancer takes a heavier toll on Black men.

Dr. Ajay Singh, a professor and vice chair for research and faculty development in the Department of Cell and Molecular Biology, is studying how chronic stress and inflammation may change the environment surrounding prostate tumors, potentially encouraging cancer growth and making treatment less effective.

Caption

The research goes beyond genetics.

Ajay Singh, also CCRI associate director of basic and translational research, is examining how environmental conditions, economic circumstances, chronic stress, lifestyle and access to quality health care may interact with a person's biology to influence cancer outcomes.

"The body responds to its environment," Ajay Singh said.

Over time, prolonged stress and other difficult life circumstances can affect hormones, inflammation, the immune system and other processes that help regulate the body.

Researchers want to know whether these changes leave biological clues that could explain why certain cancers become more aggressive.

Ajay Singh compares the relationship between cancer and its surroundings to seeds growing in soil.

Cancer cells are the seeds. The surrounding tissue and conditions within the body are the soil.

Just as the quality of soil affects how plants grow, changes in the body's internal environment may make it easier for cancer cells to grow and spread.

Years of chronic stress and other exposures, researchers believe, may help create those conditions.

"If we can identify those signals," Ajay Singh said, "we may be able to make better risk predictions and identify ways to interrupt those processes."

By identifying biological clues that help distinguish between the two, researchers hope to give physicians better tools to determine which patients need treatment sooner - and which might safely avoid unnecessary treatment and its potential side effects.

Pancreatic cancer: Finding its earliest clues

While Ajay Singh studies what makes certain cancers more aggressive, Dr. Keli Xu is investigating where one of the most difficult cancers to treat begins.

Pancreatic cancer often develops without obvious warning signs, making it difficult to detect before it reaches an advanced stage.

Xu

Xu, professor in UMMC's Department of Cell and Molecular Biology, and his team have identified a group of cells that can give rise to pancreatic tumors under certain genetic conditions.

These cells, called centroacinarcells, connect structures within the pancreas that produce digestive enzymes to the ducts that carry those enzymes.

Using models, researchers found that mutations involving a cancer-protecting gene called p53 can allow tumors to develop from these cells. They also identified a molecule called Lfng that plays a vital role in the process. When the researchers removed the gene responsible for Lfng, tumors originating from those cells did not develop.

The discovery could eventually help scientists identify ways to interrupt pancreatic cancer before it takes hold.

Xu is also collaborating with Ajay Singh to investigate whether tiny particles released by cells into the bloodstream carry early warning signs of pancreatic cancer.

The researchers are studying genetic material within these particles to determine whether it could someday help doctors detect the disease earlier through a blood test.

Another finding may prove equally important: Pancreatic tumors that begin in several types of cells can respond differently to treatment.

Xu's laboratory has identified tumors that resist certain existing cancer drugs but appear vulnerable to another experimental approach that blocks a cellular signaling pathway.

Targeting cancer where treatment is needed most

While researchers such as Xu investigate how cancers begin and which treatments may work best, others are tackling another challenge: delivering cancer-fighting drugs precisely where they are needed without unnecessarily affecting healthy tissue.

That is the problem Dr. Drazen Raucher, professor of cell and molecular biology, and Dr. Amol Janorkar, chair of the Department of Biomedical Materials Science, are working to solve.

The researchers are developing an injectable gel designed to deliver chemotherapy directly to the site of glioblastoma, an aggressive form of brain cancer.

Even after surgeons remove a brain tumor, cancer cells can remain in nearby tissue, potentially allowing the disease to return.

Their experimental material, called a hydrogel, is a soft, water-rich substance made with specially engineered proteins and collagen.

The idea is to place the gel in the space left after a tumor is removed, allowing it to slowly release chemotherapy near any cancer cells that remain.

Rather than exposing the body to a drug all at once, the approach could provide a more controlled release of medication directly where it is needed.

In laboratory studies, the researchers have shown that they can adjust how quickly the material releases chemotherapy. The released drugs entered glioblastoma cells and reduced their survival and growth.

Raucher

The findings are promising, although the approach remains experimental and will need to be tested further to show its benefit in patients.

"Developing an effective drug is only part of the challenge," Raucher said. "We also need to get it to the right place, at the right concentration, for the right amount of time."

The team is also studying specially designed protein carriers that could transport cancer-fighting drugs and respond to gentle heating at the tumor site, potentially helping concentrate more medication where it is needed.

The ultimate hope is to improve treatment effectiveness while reducing side effects.

But researchers must first establish that these methods are safe for surrounding healthy brain tissue and demonstrate their effectiveness through additional studies before they can be considered for use in patients.

Building discoveries and next generation of scientists

From uncovering pancreatic cancer's earliest beginnings to exploring how life experiences influence tumors, UMMC researchers are approaching the disease from different directions - but with a shared purpose.

Their investigations span cancer biology, population health, biomedical engineering and emerging technologies, reflecting a collaborative effort to turn scientific discoveries into better opportunities for prevention, earlier detection and more effective treatment.

The new CCRI home could strengthen those connections by bringing laboratory scientists, engineers and clinicians closer together, helping them turn scientific discoveries into potential solutions for the challenges patients face.

That collaboration is especially important in Mississippi, where cancer continues to take a heavy toll on families and communities. According to the Mississippi State Department of Health, the state's age-adjusted cancer death rate was 23% higher than the national average from 2018 to 2022.