About 10 million people die from cancer every year. It is the second leading cause of death in the US after heart disease, with more than 1,500 fatalities per day. Yet much remains unknown.
Researchers have linked certain behaviors to a higher risk of developing the disease. For example, people who smoke are more likely to have lung cancer. Those who spend a lot of time outside without sunscreen can develop skin cancer.
Scientists have long known that diet and cancer are also linked. But diet can influence more than just our likelihood of developing the disease. It can also affect how patients respond to therapies and their health during treatment.
At the Cold Spring Harbor Laboratory (CSHL) Cancer Center, scientists are working to better understand the links between cancer and diet. The hope is that their groundbreaking findings will one day lead to better patient outcomes.
What are we eating?
“The biggest challenge of our lives is figuring out what to eat,” says CSHL assistant professor and member of the Cancer Center Semir Beyaz. “Every disease that affects a majority of the human population – chronic diseases, non-communicable diseases, infections, cancer, heart disease, neurological disorders, depression – is in some way linked to the way we consume food.”
Beyaz’s laboratory studies nutrients and metabolism – how our bodies convert food into energy and building blocks. Specifically, he considers how these factors can influence our risk of developing cancer.
CSHL Assistant Professor Semir Beyaz discusses possible links between diet and disease during a recent episode of CSHLs Cocktails and chromosomes series at Industry bar in Huntington, NY.
A few years ago, Beyaz decided to delve further into the relationship between obesity and colon cancer. Previous research has shown that obesity increases the risk of developing 13 different types of cancer, including colorectal cancer.
To find out how this works, Beyaz fed laboratory mice high-fat diets and examined how these affected the relationship between intestinal cells and the immune cells that signal cancer. He found that mice that ate more fatty foods had lower levels of MHC-II, a tag that marks abnormal cells so the immune system can destroy them. Without MHC-II, problem cells that could develop into tumors went unnoticed.
Interestingly, the study indicated that obesity itself did not dampen these immune surveillance mechanisms. Instead, it was a high-fat diet. The diet appeared to disrupt gut microbes that are essential for maintaining MHC-II expression.
“There is an interaction between microbes, immune cells and stem cells that is important for the immune surveillance of tumor-initiating stem cells,” says Beyaz. “We showed that this is strongly influenced by environmental factors such as diet. Changes in cellular communication caused by diet can influence whether or not you develop cancer. That’s crazy, when you think about it.”
But both cancer and diet affect everyone differently. Could foods linked to cancer in some cases help treat the disease in others? No one can say for sure. However, having too much or too little of certain nutrients in our diets can affect these differences. Beyaz’s research led him to a specific high-fat diet known as the ketogenic diet. This diet includes meal plans that are low in carbohydrates (including sugars), moderate in protein, and high in fat.
“In some cases, it can also reduce the risk of cancer in mice,” says Beyaz. “But we don’t know if these effects are safe or generalizable to humans.”
Keto: a double-edged sword
Many health influencers tout the keto diet as an effective way to lose weight quickly. Doctors often warn that this can cause complications such as low blood pressure, kidney stones and vitamin deficiencies. But now researchers are wondering whether the keto diet could help in treatments for diseases including Alzheimer’s disease, multiple sclerosis and cancer. If doctors can maximize the diet’s potential benefits and minimize its harmful effects, better patient outcomes may be in store.
Tobias Janowitz, associate professor and member of the Cancer Center, recently studied keto’s impact on cancer. Because tumors require glucose to grow, it has been suggested that the low-sugar keto diet could slow their spread. Janowitz’s lab focuses on cancer as a whole-body disease that affects normal processes. His team wondered: if keto slowed tumor growth, how might this affect the metabolic process of cancer patients. In particular, would it slow or accelerate a dangerous side effect of cancer, the wasting disease called cachexia?
Cachexia occurs in approximately 80% of patients with advanced cancer and directly causes approximately 30% of cancer deaths. When it comes to pancreatic cancer, it is estimated that as many as 80% to 90% of patients will experience cachexia at some point. The condition causes rapid weight loss, among other debilitating symptoms.
“It has a major negative impact on the quality of life because patients suffer from it,” says Janowitz. “They lose energy. They lose functional body mass: muscle and tissue. And it makes them less resistant to treatment options.”
Researchers in the Janowitz lab tested the relationship between keto, cancer and cachexia using mice genetically predisposed to pancreatic and colorectal cancer. They found that the diet seemed like a double-edged sword. Although it slowed tumor growth, the mice died sooner because the diet accelerated the onset of cachexia. Mice with cancer cannot produce enough of the hormone corticosterone, which helps regulate the effects of keto. These mice continued to lose weight, while healthy mice adapted to the diet and their weight eventually plateaued.
The researchers wondered if they could counteract this effect and tested whether the depleted corticosterone could be replaced with a commonly used drug called corticosteroids. The test worked. In mice treated with both steroids and keto, the tumors shrank and the animals did not experience cachexia.
“Cancer reprograms normal biological processes to help it grow,” explains laboratory researcher Miriam Ferrer Gonzalez. “This reprogramming causes mice to be unable to utilize the nutrients from a keto diet and to waste away. But with the steroid they did much better.”
Don’t forget your vitamins
Like the pancreatic and colorectal cancers Janowitz studies, leukemia reprograms biological processes, including metabolism. A few years ago, CSHL assistant professor and Cancer Center member Lingbo Zhang wanted to better understand how acute myeloid leukemia (AML) grows and spreads so quickly in patients’ bodies. This type of blood cancer is known to be particularly aggressive. Zhang thought if he could figure out how the cancer works so quickly, he might be able to slow it down. And that could point the way to better patient outcomes.
Zhang identified 230 metabolic genes that are highly active in leukemia cells compared to healthy cells. Then, using the gene-editing tool CRISPR, he disabled each gene one by one to see if this would stop cancer cells from multiplying. Zhang discovered that a gene that produces an enzyme called pyridoxal kinase (PDXK) is most important for the growth of leukemic cells.
In healthy cells, PDXK regulates the activities of vitamin B6, which is required for more than 100 enzyme reactions involved in metabolism. However, because cancer cells divide more frequently than normal cells, PDXK continually stimulated B6 activity. This increased activity is fueling AML growth.
CSHL Assistant Professor Lingbo Zhang sheds light on leukemia’s addiction to vitamin B6, an essential nutrient for the health of the nervous and immune systems.
“Compared to normal cells, leukemic cells are addicted to vitamin B6,” says Zhang. “This addiction provides a therapeutic window to selectively target the leukemic cells.”
In contrast to Janowitz and Beyaz’s research, Zhang’s studies do not directly focus on dietary changes. After all, regular vitamin B6 activity is necessary for the survival of healthy cells. Instead, Zhang and his colleagues want to help develop a drug that specifically blocks leukemia from activating PDXK. By manipulating the way the enzyme controls B6 activity, a drug can slow or even stop the growth of cancer cells. And this could happen without the potential side effects that could result from cutting out vitamin B6 completely.
From Zhang’s lab to research benches at the Cancer Center and across CSHL, scientists agree that the food we eat powers our body and determines how it functions. They know that malnutrition and poor food choices can increase our risk of developing a variety of diseases, including cancer. By studying the links between whole-body health, cancer and nutrition, CSHL scientists can bring us closer to new prevention strategies and therapies that will change the way we treat a wide range of diseases.
There is a long road between successful preclinical studies in laboratory mice and new nutritional recommendations or treatment regimens for humans. Yet the goal remains clear. Scientists at the CSHL Cancer Center hope that their basic biology research will one day lead to better patient outcomes.
“Your future is what you eat,” says Beyaz. “Hopefully we make our future healthy.”
Editor’s Note
This article should not be used as a guide to clinical practice or health-related behavior. The article reports results from preclinical research in mice, not clinical trials. All content is for informational purposes only and should not be considered medical advice.
Written by: Margaret Osborne, Scientific writer | publicaffairs@cshl.edu | 516-367-8455