Huang Lab Awarded Owens Medical Research Foundation Grant

Gang Huang, PhD, professor in the Departments of Cell Systems and Anatomy and Pathology and Laboratory Medicine; holder of the Kathryn Mays Johnson Distinguished Chair in Oncology; associated with UT Health San Antonio's Mays Cancer Center, received funding from the William and Ella Owens Medical Research Foundation for the following project.

Project: The role of the Warburg effect on cellular and systemic energy metabolism in PDAC cachexia

Synopsis: Pancreatic ductal adenocarcinoma, or PDAC, is one of the deadliest types of cancer and is often diagnosed in its later stages. A common and very serious problem that the majority of PDAC patients face is called cancer-associated cachexia, or CAC—a profound weight loss and muscle wasting condition that not only weakens patients but also makes treatments less effective. CAC-induced organ failure is the primary cause of death in patients with advanced cancer, and unfortunately, there are no FDA-approved treatments for the condition.

This project investigates how the loss of a key regulator gene, called LKB1 or STK11, in PDAC cells leads to a chain reaction in the body's energy use, known as the Warburg effect. In healthy cells, LKB1 helps maintain balanced energy production by activating AMPK. When LKB1 is missing, cancer cells accelerate their sugar-burning processes (glycolysis), while reducing fat-burning processes like fatty acid oxidation and other energy-generating pathways. This shift forces the tumor to use up large amounts of glucose, lowering blood sugar levels throughout the body. As a result, the patient's muscles and fat stores are broken down to compensate, contributing to the severe weight loss seen in cachexia. Eventually, this unintentional weight loss leads to weakness, fatigue, anorexia, pain, depression and systemic organ failure.

By pinpointing the exact molecular events that drive this imbalance in both cells and animal models, researchers aim to develop new therapies that block the tumor's hijacking of the body's energy stores.