Using an eIF4A Inhibitor to Exploit a Metabolic Vulnerability Created by Epigenetic Therapy of Pancreatic Cancer

Pancreatic cancer (ductal adenocarcinoma) is characterized by cancer-inducing, activating KRAS mutations that support the growth and survival of a tumor with one of the fastest growth rates among human solid tumors. Among the functions of mutant KRAS is inducing reprogrammed metabolism, the breakdown of nutrients for energy, via several downstream pathways. Dr. Bates and her team have identified a strategy that interferes with the high metabolic need of pancreatic cancer cells by systematically depleting essential nutrients from the cancer cells. The goal is starvation of nutrients that will lead to cancer cell death. This strategy is based on the interaction of two drugs that work together to lethally interfere with cellular metabolism. Early experiments have suggested that the drugs are synergistic, which means their combined effect is stronger than adding each individual drug's effect together.