Restricting Dietary Sugars Improves the Treatment of Colorectal and Small Intestine Cancers

Background & Unmet Need

• Colorectal cancer (CRC) is the third most common type of cancer in the world
• A high fructose diet is connected to cancer and obesity, the two largest causes of mortality
• The mechanism of why high-fructose corn syrup (HFCS) leads to worse cancer outcomes was previously unknown
• HFCS is converted to a carcinogen, fructose 1-phosphate (F1P), by ketohexokinase (KHK)
• F1P is structurally similar to fructose 1,6-bisphosphate (FBP), an inhibitor of PKM2 gene, and promotes hypoxia
• Unmet Need: Improved understanding of the impact of dietary sugars on cancer, to inform dietary recommendations and targeted therapies

Technology Overview

• The Technology: Method to reduce or eliminate sugar from diet or administer a treatment targeting the fructose-uptake pathway to inhibit or reduce onset of colon and intestinal cancers
• The Discovery: Specific molecules in the fructose-uptake pathway are upregulated in high-fat diets and promote tumor growth and incidence
• PoC Data: In mice models, HFCS enhances tumor growth by promoting hypoxic cell survival, as evidenced by the presence of longer intestinal cell villi (Fig. 1)
• Small molecules that target upregulated proteins in the fructose-uptake pathway (HPK, GLUT5, P3K, PKM2) prevent cancerous phenotypes, including longer villi length in intestinal cells and prolonged cell survival that increase adiposity in mice (Fig. 2)
• Making dietary changes to reduce fructose levels or pharmacologically targeting the fructose-uptake pathway may thus improve treatment outcomes

Technology Applications

• Restriction of dietary sugars (e.g., sucrose, fructose) may reduce the risk of oncogenesis in patients at high risk of developing colorectal cancer
• Special meal kits for cancer patients with reduced amounts of the identified sugars and proteins
• Administering inhibitors of GLUT5, KHK, FASN, PI3, or PKM2 activator to reverse cancer progression in individuals with high-sugar diets

Technology Advantages

• Dietary changes can be implemented immediately and are a low-cost option
• Drug candidates already exist for several genes in fructose-uptake pathway: PHGDH, GLUT5, KHK, FASN, PI3 kinase