What if the sugar we consume, or even the sugar our own bodies produce, could increase the risk of cancer?
That’s the question driving groundbreaking research by Hyeyoung Nam, Ph.D., instructor in the UAB Department of Urology, who was recently honored with a Department of Defense (DoD) Concept Award for her study, “The Polyol Pathway Promotes Renal Cancer Tumorigenesis via Glucose-mediated Lipogenesis.”
This proposal investigates how both dietary sugar and sugar produced within the body may fuel the development of renal (kidney) cancer. The DoD Concept Award is designed to support innovative, high-risk research with the potential to transform cancer prevention and treatment.
A closer look at sugar, obesity, and cancer
Excessive sugar consumption is well known to contribute to weight gain and obesity. In fact, the National Cancer Institute recently concluded that obesity is associated with an increased risk of 13 types of cancer, including renal cancer. Additionally, recent studies have indicated that excessive fructose intake may increase the risk for both obesity and colorectal cancer.
“While most research to date has focused on the metabolic effects of dietary fructose increases tumorigenesis or cancer development, a critical detail is often overlooked,” Nam explained. “Fructose can also be generated endogenously from glucose through the polyol pathway. Recent findings suggest that this pathway plays a significant role in activating lipogenesis, a key process in cancer development.”
The polyol pathway
With support from the award, Nam’s research focuses on the polyol pathway, a lesser-known metabolic process through which the body converts glucose into fructose through two steps. First, glucose is reduced to sorbitol by the enzyme aldose reductase (AKR1B1), and then sorbitol is oxidized into fructose.
“While this pathway is known to influence lipid metabolism, its role in cancer has received far less attention,” she stated. “However, data from the Clinical Proteomic Tumor Analysis Consortium shows that AKR1B1 is highly expressed in renal cancer, suggesting it could be a driver of tumorigenesis.”
Nam’s research aims to clarify this connection by investigating whether the polyol pathway actively contributes to renal cell carcinoma (RCC) development. Her findings could open the door to novel therapeutic strategies, including glucose-restricted diets and pharmacological inhibitors that block the polyol pathway to suppress growth.
“A better understanding of the molecular mechanisms underlying polyol pathway-mediated tumorigenesis is essential,” she said. “We believe this work will offer valuable insights into the mechanistic connection between obesity and cancer. Importantly, results will determine the viability of targeting the polyol pathway as a therapeutic strategy for RCC cancer patients.”