Talk like a translational cancer researcher

Gut microbiome — the combination of microorganisms (e.g., bacteria, viruses, fungi) that live in the gut and support digestion, immunity and overall health

Mediterranean diet — a diet high in healthy fats, such as olive oil and fish oil

Probiotic — a supplement (commonly found in yoghurt) containing live, beneficial microorganisms that support a healthy gut microbiome

Receptor — a structure on or inside a cell that attaches to specific molecules, such as hormones, and triggers a response in the cell

Translational research — a combination of lab-based and clinical research, with results from each informing the other

Western diet — a diet high in unhealthy saturated fats, sugar and salt

When Dr Katherine Cook was eight, her grandmother passed away from breast cancer. A few months later, Katherine’s aunt was also diagnosed with the disease. And since then, both Katherine and her mother have had surgery after discovering lumps in their breasts.

Katherine and her family are not alone. In most countries, breast cancer is the most common form of cancer in women. And in the US, 1 in 8 women will be diagnosed with breast cancer during their lifetime. “My own experience, coupled with my family history, has served as motivation for my career as a breast cancer researcher,” says Katherine. She conducts translational research at Wake Forest University School of Medicine to study how the gut microbiome interacts with breast cancer therapies.

What is the gut microbiome?

Your gut contains trillions of microscopic organisms, including bacteria, viruses and fungi. Together, they are known as the gut microbiome and play a vital role in keeping you healthy. “In a healthy person, these microorganisms live within us in a balanced state,” explains Katherine. “Your gut microbiome helps you digest the food you eat, generates vitamins to support your health, helps your immune system function, and protects you from infections.” Lifestyle factors, such as diet and medications, affect the health of your gut microbiome which, if it becomes unbalanced, can affect the health of the whole body.

How is the gut microbiome relevant to cancer research?

Some breast cancer patients are given oral medication that is absorbed into the body from the gut. This means the drugs will interact with the microorganisms in their gut, and Katherine wants to understand how this impacts the outcome of cancer treatment. Other patients are given immunotherapy – drugs that stimulate the immune system to kill cancer cells. “As the gut microbiome influences immune cell activity, it impacts immunotherapy efficacy,” explains Katherine. To explore these issues, Katherine is analysing faecal samples from breast cancer patients.

Why are faecal samples useful?

“Everybody poops!” says Katherine. “Faecal samples are non-invasive biospecimens that could help us determine whether a patient will respond to their therapies.” Patients in Katherine’s clinical trials collect faecal samples and send them to Katherine’s lab, where she analyses the DNA they contain. This allows her to determine what bacteria are present in the faeces and, therefore, in the gut microbiome. “We can then use this information to understand how the bacteria may be influencing the patient,” she explains.

How is Katherine conducting clinical trials?

In one trial, Katherine is researching hormone receptor-positive (HR+) breast cancer. This is the most common type of breast cancer, in which cancer cells have receptors that respond to oestrogen and progesterone. These hormones help the cancer to grow, so treatment involves drugs that reduce the hormones’ ability to send signals to the receptors.

Katherine is collecting faecal samples from patients before they start treatment and after one and three months of taking the drugs. “We will sequence DNA isolated from the samples and measure how the bacterial species change when HR+ breast cancer patients start therapy,” she says. “Some types of bacteria may affect how therapies are excreted from the body, which could change the drug bioavailability (the amount that enters the body).”

In another trial, Katherine is researching triple-negative breast cancer (TNBC), a type of breast cancer that is more common in young and minority women. It requires a different type of treatment because the cancer cells lack hormone receptors, so patients are treated with a combination of chemotherapy (drugs that kill cancer cells) and immunotherapy.

Katherine is collecting faecal samples, blood samples and diet information from TNBC patients before and after they complete their treatment. “We aim to investigate if certain diets or gut microbiome species are associated with better health outcomes,” she says.

Why is translational research important?

In addition to her clinical trials, Katherine uses mouse models to test her clinical observations in the lab. “For example, if we identify bacteria that are enriched in the gut microbiome of breast cancer patients, we can feed these bacteria to mice with tumours,” she says. “This allows us to determine whether these bacteria may promote tumour growth or increase anti-cancer outcomes.”

Each discovery informs the next stage of Katherine’s work. By understanding how diet, the gut microbiome and cancer therapies interact, Katherine can design future clinical trials to test whether key dietary features could improve patients’ outcomes. “For example, if our clinical trial identifies that TNBC patients who eat at least 25 grams of fibre a day respond better to chemotherapy and immunotherapy, then we could design a study to determine whether fibre improves anti-cancer efficacy,” explains Katherine.

What has Katherine discovered?

Katherine’s clinical trials are still ongoing, but she has already made exciting discoveries from her lab-based research. She has shown that, if mice are fed an unhealthy Western diet, a probiotic made from the bacterium Lactobacillus improves the effectiveness of drugs to prevent HR+ breast cancer from recurring. “We have also demonstrated that mice with TNBC tumours respond better to immunotherapy if they are fed a Mediterranean diet rather than a Western diet,” she says. “In our clinical trial, we are now investigating whether women who eat more healthy fats respond better to immunotherapy.”

Katherine hopes her research findings will improve outcomes for future breast cancer patients. “Ultimately, I want our studies to improve clinical care to reduce breast cancer related deaths.”

Dr Katherine Cook
Associate Professor, Department of Cancer Biology, Wake Forest University School of Medicine, USA

Field of research: Translational breast cancer research

Research project: Analysing faecal samples to investigate how the gut microbiome interacts with breast cancer therapies

Funders: US National Cancer Institute (NCI); Department of Defense (DOD) Congressionally Directed Medical Research Program (CDMRP); metaVIVOR; The V Foundation

About translational cancer research

“Translational research bridges the gap between basic science and clinical practice to develop practical applications that will directly benefit patients,” says Katherine. Translational cancer researchers use lab-based methods and clinical trials to explore questions such as how cancer cells grow, how the immune system reacts and, in Katherine’s case, how the gut microbiome and diet might affect treatments. Answering these questions will lead to more effective prevention strategies and better therapies.

From bench to bedside and back again

“Translational research is defined as the ability to move scientific discoveries from the lab into the clinic for testing to develop real life applications,” says Katherine. This is often known as the ‘bench-to-bedside-to-bench approach’, where researchers make discoveries in the lab, then see if these apply in human testing, and then take the results of clinical trials back to the lab to build on them further.