Cholesterol is an essential lipid that plays a critical role in hormone production, digestion, and immune function. The ability to maintain a balanced level of cholesterol — known as cholesterol homeostasis — can influence tumor growth, progression, and immune response. High cholesterol levels have been associated with poor cancer prognosis.
A new review paper from the lab of Erik Nelson, a professor of Molecular & Integrative Physiology, provides an in-depth summary of the research linking cholesterol metabolism, cancer progression, and immune therapy. Their review appears in Endocrinology.
“We are interested in unraveling how cholesterol homeostasis might modulate immunity to fight against cancer,” said Yu (Amber) Wang, a graduate student in Molecular & Integrative Physiology and the co-first author of the paper. “This is the first piece of literature comprehensively summarizing the field.”
Wang and Shruti Bendre, graduate students in Molecular & Integrative Physiology and co-first authors of the paper, spoke to the School of MCB Communications Office about cholesterol metabolism, its effect on the tumor microenvironment, and what is still left to be learned.
Why is your lab interested in the relationship between cholesterol and cancer progression?
Wang: We know that cholesterol regulators play a role in maintaining intracellular homeostasis, which allows them to be expressed in all types of cells, including immune cells. Our lab had found that modulating cholesterol homeostasis can regulate immune response within tumor microenvironment, and we wanted to extrapolate on that.
How will this information benefit other researchers?
Wang: We noticed that the entire field was lacking a thorough review of up-to-date research findings. Our goal was to consolidate the findings from other scientists — including ourselves — into a comprehensive summary. This review can function as a good starting point for future researchers, because it highlights both what has already been discovered and the areas that still require further exploration.
How will this information benefit cancer patients?
Bendre: Lifestyle plays an important role in cancer progression, and a major component of lifestyle is diet. A lot of clinical findings have linked statins — a class of drugs commonly prescribed to lower blood cholesterol levels — to increased overall survival and lower risk of breast cancer recurrence. So there is huge clinical importance.
The Nelson Lab focuses on breast cancer research. What are the limitations of current breast cancer treatment options and why is there a need for alternative treatments?
Wang: Metastasis is the one of the primary causes of death among breast cancer patients, and we want to develop a treatment that could prevent or slow metastasis. Currently we are lacking an effective approach to target metastasis.
Bendre: The current treatment options for metastatic breast cancer are very limited. There are very few targeted therapeutics, especially in the late stages of disease. There have been recent developments in immunotherapy, but the qualifying criteria is very narrow. A lot of patients grow refractory, which means they stop responding to treatment or become resistant. So there is a need to develop better immunotherapy targets.
What is still unknown about cholesterol metabolism and its relationship to cancer progression?
Wang: There are a lot of contradictory findings in the literature. One study may demonstrate that a cholesterol regulator has anti-tumor effects, while another study may show the opposite. Several key cholesterol regulators we identified remain underexplored, and there is still little understanding of their roles.
What is your main takeaway from this review?
Bendre: We know there can’t be a one-size-fits-all target for cancer therapy. We have to ensure that targeted therapies behave in a way that is specific to each patient’s disease.
Editor’s note: this research was supported by funding from the National Institutes of Health and the Department of Defense.
