April 26, 2016
Our scientists have found that blocking one molecular pathway could make pancreatic cancer susceptible to formerly ineffective therapies. “While there’s more work to be done to confirm the results in pre-clinical models and then humans, we are encouraged by these preliminary results,” said Jonathan Brody, PhD, a researcher at our Sidney Kimmel Cancer Center and Director of Surgical Research at TJU.
Pancreatic cancer is on track to become the second leading cause of cancer-related deaths by 2020. These statistics are due, in part, to pancreatic cancer’s resistance to most targeted cancer therapies. Working with pancreatic cancer cells, researchers have now found a mechanism that could be responsible for the cancer’s resistance to at least one targeted approach. If the results hold true in animal models and eventually clinical trials, the approach could help researchers develop more effective combination therapies and breathe new life into forgotten and failed cancer drugs.
“We’ve teased out one mechanism behind pancreatic cancer cells’ resistance to certain drugs,” said Jonathan Brody, PhD, a researcher at our Sidney Kimmel Cancer Center and Director of Surgical Research at TJU. “Knocking out this resistance mechanism could make pancreatic cancer vulnerable to therapies that had great promise in the past. While there’s more work to be done to confirm the results in pre-clinical models and then humans, we are encouraged by these preliminary results.”
For years, researchers and pharmaceutical companies had worked on a cancer therapy that functioned by activating the so-called “death receptor” on cancer cells. The researchers could quickly cause the cancer cells to self-destruct by “turning on” this receptor using a synthetic mimic of a naturally occurring compound called TRAIL (Tumor necrosis factor-Related Apoptosis Inducing Ligand). However, when tested in human tumors, TRAIL-mimicking drugs performed poorly, usually because the cancer cells quickly became resistant to this therapeutic strategy.
In results published online April 6 in the journal Molecular Cancer Research, Dr. Brody and colleagues showed that a protein called HuR (Hu antigen R) is a hub for cancer cell survival and drug resistance, especially when pancreatic cancer cells are treated with TRAIL. Treated cells activate HuR, which then reduces the amount of death receptors available for TRAIL to bind. Simply put, the fewer death receptors or triggers, the less effective the TRAIL-mimicking drugs become.
Learn more — see the news release on Jefferson.edu.