Researchers at Jonsson Comprehensive Cancer Center (University of California-Los Angeles) have identified a potential treatment for pancreatic cancer by using two types of drug inhibitors simultaneously. The new approach uses one drug that inhibits cancer cells’ ability to recycle essential nutrients to survive (lysosome) and another drug that blocks the pathway used to repair DNA.
The lack of effective treatments for pancreatic cancer–the third leading cause of cancer-related deaths in the U.S.–indicates a limited understanding of the disease’s biologic complexity and the mechanisms to explain why pancreatic cancer often becomes resistant to therapies that work for other cancers.
Researchers studied two sets of data to try to understand the mechanism of lysosome-dependent pathways. Taking chloroquine, which is used to treat malaria, they combined it with more than 500 different inhibitors to screen for any unexplored interactions that could yield a "synergistic" effect. This led to the researchers finding a complementary inhibitor called replication stress response inhibitor.
Secondly, the team measured metabolites in pancreatic tumor cells that were treated with chloroquine alone. They found the drug causes a reduction in aspartate, which synthesizes nucleotides, crucial for the repair and replication of DNA.
The study showed that combining chloroquine with an inhibitor of the replication stress response pathway could be a new treatment for reducing tumor growth in patients with pancreatic cancer and help improve patients’ prognosis.
The research has been published in the Proceedings of the National Academy of Sciences.
Source: MedicalXpress, March 20, 2019