Research News

What started as a personal investigation into diet and metabolism led Cancer Biology postdoctoral fellow Ashley E. Holly, PhD, MBA, to a recent honor: the Prostate Cancer Foundation’s “Young Investigator Award.” 

The award is designed to jump-start new ideas in prostate cancer research and will support an upcoming clinical trial on dietary interventions in prostate cancer. Patients with prostate cancer often experience severe metabolic dysfunction, which can lead to or exasperate other conditions. This rigorous research, where all participant meals are provided for tighter scientific control, is translational research which can contribute to evidence-backed nutrition information for patients to discuss with their doctors before or during treatment – or just to improve overall health.

“Patients don’t know where to start,” Dr. Holly says. “That’s such a huge challenge that actually prevents people from starting to use diet as a tool.”

Dr. Holly, who earned her PhD in regulatory biology through a joint program at Cleveland State University and Cleveland Clinic Lerner Research Institute, began integrating nutrition and wellness into her career after she started making small changes in her own life and seeing major differences. Drastic dietary changes are overwhelming for anyone, she says, which is why generally it’s better to start small.

The prostate cancer trial, for example, examines whether a low-fat or lower-carb version of the same diet leads to more favorable changes in host and prostate tissue metabolism. Both diets are based on a Mediterranean Diet, which is nutrient-dense and focused on whole foods. The Mediterranean Diet is already shown to reduce the risk of heart disease and stroke. From there, the diets are altered to be either higher-fat or high-carb.

To avoid drastic challenges to diet and make sure patients are comfortable, the trial is designed to accommodate food preferences, including cultural, to meals. Participants have some choices for what the meals include, like spinach versus collard greens, without compromising the scientific basis of the dietary interventions. These choices and sending spices to make meals more flavorful makes the changes a little more accessible, Dr. Holly says.

A personal journey to an emerging field

Interest into how diet can affect diseases like cancer is growing, stemming from a recent deeper understanding of cancer metabolism and the microbiome, Dr. Holly says. She works in the lab led by Nima Sharifi, MD, Cancer Biology and Director of Genitourinary Malignancies Research, which focuses on fundamental metabolism processes that lead to cancer progression and resistance to medical therapies.

“Though nutrition is an invaluable tool for doctors and patients, the science behind it wasn’t always, and still isn’t, fully understood,” Dr. Holly says. “But drastic changes associated with diet and microbiome paved the way for more rigorous research into how nutrition can positively affect patients.”

Cancer metabolism refers to how cancer alters the processes cells use to turn nutrients into energy to grow and multiply. The microbiome is made up of trillions of bacteria that live on and in humans. A growing body of research shows how bacteria in the gut, which are responsible for processing these nutrients from food, can affect health and diseases.

Dr. Holly launched her own scientific consulting business in 2016, working with clients focused on the application of nutrition as a therapeutic, optimizer of overall health, and enhancer of human performance. Before beginning at University of Texas’ MD Anderson Cancer Center, she wrote scientific articles and commentary on ketogenic diets, which are high-fat, moderate protein, and very low carbohydrate and shown to be beneficial for some medical conditions.

“I firsthand saw the power of diet as medicine,” she said. “There are applications for drugs and other medical therapies, but there’s a lot we can do with diet and physical activity.”

At MD Anderson, Dr. Holly was part of a team that performed rigorous early phase (I and II) controlled dietary intervention trials in melanoma, examining how changes can coordinate with immunotherapy. After earning her MBA, she then returned to Cleveland and started her postdoctoral fellowship in the Sharifi Lab in September 2021.

The upcoming clinical trial takes previous dietary studies to the next level of evidence by providing all the meals and collecting longitudinal specimens and assessments for deep metabolic interrogation, Dr. Holly says.

“Most diet-based studies are behavioral or observational – you’ve either done it retrospectively by looking back at patient charts or you tell patients what to eat,” she says. “This is a high-impact trial and controlled study – something this field and any research area desperately needs.”