Approximately 10 million people die from cancer every year. It is the second leading cause of death in the United States, behind heart disease, with more than 1,500 deaths occurring there every day. However, much about this is unknown.
Researchers have linked certain behaviors to a higher risk of contracting the disease. For example, people who smoke have a higher risk of lung cancer. People who spend too much time outside without sunscreen may develop skin cancer.
Scientists have long known that nutrition and cancer are also linked. But diet can affect more than just our likelihood of developing disease. It can also affect how patients respond to treatments and their health while they are receiving treatment.
At Cold Spring Harbor Laboratory (CSHL) Cancer Center, scientists are working to better understand the connections between cancer and nutrition. The hope is that their groundbreaking findings will one day lead to better patient outcomes.
What’s for dinner?
“The biggest challenge of our lives is deciding what we should eat,” says CSHL Assistant Professor and Cancer Center member Semir Beyaz. “Every disease that affects the majority of the human population (chronic diseases, non-communicable diseases, infections, cancer, heart disease, neurological disorders, depression) has a connection to the way we consume food.”
White’s lab studies nutrients and metabolism—how our bodies convert food into energy and building blocks. It specifically addresses how these factors may affect our risk of developing cancer.
CSHL Assistant Professor Semir Beyaz discusses possible connections between diet and disease in the latest episode of CSHL Cocktails and Chromosomes series at Industry bar in Huntington, NY.
A few years ago, White decided to take a deeper look at the relationship between obesity and colorectal cancer. Previous research has shown that obesity increases the risk of developing 13 different types of cancer, including colorectal cancer.
To understand how this works, White fed laboratory mice high-fat diets and studied how they affected the relationship between intestinal cells and immune cells that signal cancer. He found that mice that ate more fatty foods had lower levels of MHC-II, a tag that signals abnormal cells that the immune system should destroy. Without MHC-II, problematic cells that could develop into tumors went unnoticed.
Interestingly, the study showed that obesity itself does not inhibit these immune surveillance mechanisms. A high-fat diet was followed instead. The diet appeared to disrupt gut microbes necessary for maintaining MHC-II expression.
“There is cross-talk between microbes, immune cells, and stem cells that is important for immune surveillance of tumor-initiating stem cells,” says White. “We’ve shown that this is greatly influenced by environmental factors such as nutrition. The change in cellular communication through diet can affect whether you get cancer. It’s crazy if you think about it.”
But both cancer and diet affect everyone differently. Could foods that may be linked to cancer in some cases help treat cancer in others? No one can say for sure. However, too much or too little of some nutrients in our diet can affect these differences. White’s research led him to a 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 whether 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 deficiency. But now researchers are wondering whether the keto diet could help treat diseases such as Alzheimer’s, multiple sclerosis and cancer. If doctors can maximize the diet’s potential benefits and minimize its harmful effects, better patient outcomes may be on the horizon.
CSHL Associate Professor and Cancer Center member Tobias Janowitz recently studied the effect of ketone on cancer. Since tumors need glucose to grow, it is suggested that a low-sugar keto diet may slow their spread. Janowitz’s lab focuses on cancer as a disease that affects normal processes throughout the body. His team wondered how ketone might affect the metabolic process of cancer patients if it slowed tumor growth. Specifically, does it slow or accelerate the debilitating disease called cachexia, a dangerous side effect of cancer?
Cachexia occurs in approximately 80% of advanced cancer patients and directly causes approximately 30% of cancer deaths. In the case of pancreatic cancer, it is estimated that 80% to 90% of patients will experience cachexia at some point. This condition causes rapid weight loss along with other debilitating symptoms.
“It has a huge negative impact on quality of life as patients suffer from it,” Janowitz says. “They lose their energy. They lose functional body mass (muscle, tissue). “This 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 dieting appears to be a double-edged sword. Despite slowing tumor growth, the mice died earlier because the diet accelerated the onset of cachexia. Mice with cancer don’t get enough of a hormone called corticosterone, which helps regulate the effects of ketone. While these mice continued to lose weight, healthy mice adapted to the diet and their weight eventually stabilized.
Wondering if they could counteract this effect, researchers tested whether depleted corticosterone could be replaced with a common drug called a corticosteroid. The test worked. In mice treated with both steroids and keto, tumors shrank and the animals did not experience cachexia.
“Cancer reprograms normal biological processes to help it grow,” explains laboratory researcher Miriam Ferrer Gonzalez. “Because of this reprogramming, the mice are unable to use and waste nutrients on the keto diet. But they did much better with steroids.”
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 that if he could figure out how cancer works so quickly, he could slow it down. This could point the way to better patient outcomes.
Zhang identified 230 metabolic genes that were very active in leukemia cells compared to healthy cells. Then, using the gene-editing tool CRISPR, he turned off each gene one by one to see if it would stop the cancer cells from multiplying. Zhang found a gene that produces an enzyme called pyridoxal kinase (PDXK) that is most important for leukemic cell growth.
In healthy cells, PDXK governs the activities of vitamin B6, which is essential for more than 100 enzyme reactions involved in metabolism. However, because cancer cells divide more frequently than normal cells, PDXK was constantly challenging B6 activity. This increased activity is accelerating AML growth.
CSHL Assistant Professor Lingbo Zhang sheds light on leukemia’s dependence on vitamin B6, a vital nutrient for nervous and immune system health.
“Compared with normal cells, leukemic cells are dependent on vitamin B6,” says Zhang. “This dependence provides a therapeutic window to selectively target leukemic cells.”
Unlike Janowitz and White’s research, Zhang’s studies do not focus directly on changes in diet. After all, regular vitamin B6 activity is necessary for the survival of healthy cells. Instead, Zhang and his colleagues aim to help develop a drug that specifically blocks leukemia from activating PDXK. A drug can slow or even stop cancer cell growth by changing the way the enzyme manages B6 activity. And it could do this without the possible side effects that can arise from completely stopping vitamin B6.
From Zhang’s lab to the research benches at the Cancer Center and CSHL, scientists agree that the food we eat powers our bodies and determines how they function. They know that malnutrition and poor dietary choices can increase our risk of various diseases, including cancer. By studying the connections between whole-body health, cancer, and nutrition, CSHL scientists can bring us closer to new prevention strategies and treatments that transform the way we treat many diseases.
There’s a long way to go between successful preclinical experiments on laboratory mice and new dietary recommendations or treatment regimens for humans. However, the target is still clear. CSHL Cancer Center scientists hope their basic biology research will one day lead to better patient outcomes.
“Your future is what you eat,” says Beyaz. “Hopefully, we will make our future healthy.”
Editor’s Note
This article should not be relied upon to guide clinical practice or health-related behavior. The paper reports results from preclinical studies in mice, not clinical trials. All content is for informational purposes only and should not be considered medical advice.
written by:Margaret Osborne, Science Writer | publicaffairs@cshl.edu | 516-367-8455