SC Connecticut News

Rachel Perry, PhD, assistant professor of medicine (endocrinology) and of cellular and molecular physiology, initiated her lab in 2018 with a focus on understanding how systemic metabolism tools could be applied in the context of cancer. "We’re looking at how can we change the nutrients that we take in and the energy that we put out,” Perry stated. She expressed an interest in discovering ways to modify exercise or other behaviors to enhance our body's metabolic or nutritional response to cancer.

In a recent interview, Perry explored the connection between insulin and cancer, shared surprising findings from her research, and discussed the future of precision medicine for metabolism-related cancers.

Cancer cells divide rapidly, necessitating a large supply of nutrients for tumor growth. Glucose is one such major nutrient. Research indicates that insulin, a hormone produced by the pancreas, plays a crucial role in regulating glucose uptake into tumors. Insulin instructs various cells in the body to absorb glucose following a meal for energy utilization.

People with obesity often exhibit insulin resistance, meaning their cells do not absorb glucose in response to insulin. This prompts our bodies to produce more insulin to compensate for this resistance. Insulin serves as both a growth factor and a metabolic factor in cells. It directs tumor cells to absorb glucose just as it does liver and muscle cells.

However, unlike other body cells, tumor cells do not develop insulin resistance. In individuals with obesity and insulin resistance, tumor cells continue absorbing more glucose in response to insulin while other body cells do not. When insulin levels are high and other cells are unresponsive, more glucose is directed into tumor cells.

Several studies suggest that low-carbohydrate diets and exercise can reduce the risk of developing this type of cancer.

Perry's research has yielded some unexpected results. "We did a study in preclinical models where we combined a drug called dichloroacetate, which can activate glucose oxidation, with immunotherapy. We thought that if you activate glucose metabolism, it could improve the response to immunotherapy. The drug didn't slow tumor growth, but it did reduce cancer-related fatigue," she explained.

Perry was not anticipating this direction towards cancer-related fatigue, but she maintains a philosophy of following the science. A significant 90% of cancer patients report substantial fatigue that impairs their quality of life and reduces the likelihood of completing cancer treatment. Currently, there are no effective medications for this debilitating condition. Perry hopes that dichloroacetate could potentially aid these patients.

Regarding the future of treatment for metabolism-related cancers, Perry stated that the CDC has associated 13 tumor types with obesity. However, metabolic dysfunction can occur in individuals with a BMI under 30, and conversely, those with a BMI over 30 may not have metabolic dysfunction. "One key thing that we need to do is nuance our understanding of what obesity means and link tumor factors to metabolic dysfunction rather than BMI," she emphasized.

The team is striving to understand more about how systemic metabolism influences the immune response to cancer and the tumor's metabolic response to cancer. They aim to repurpose metabolic drugs used for diabetes or obesity to potentially enhance cancer treatment.

A few years ago, Perry published a paper demonstrating that various breast cancer preclinical models respond differently to insulin-lowering therapies depending on their genetic makeup. This research paves the way for developing precision medicine-type approaches using metabolic therapy for cancer.

Yale School of Medicine’s Section of Endocrinology and Metabolism aims to improve health outcomes for individuals with endocrine and metabolic diseases by advancing scientific knowledge, applying new information to patient care, and training future physicians and scientists in this field.