Old Chemotherapy Drug Effective Against Pancreatic Cancer, Study Reveals
A recent study published in the journal Proceedings of the National Academy of Sciences indicates that a common chemotherapy supplement called folinic acid weakens cancer’s defenses in pancreatic ductal adenocarcinoma (PDAC).
The battle against cancer resembles an arms race, with immunotherapy emerging as one of the most powerful tools available to clinicians. Immune checkpoint therapy has become a standard treatment for various cancers. Nevertheless, it often proves ineffective for the majority of patients with pancreatic ductal adenocarcinoma (PDAC).
Previously, it was believed that pancreatic ductal adenocarcinoma did not provoke an immune response, however, recent researchers have proved that immune cells do indeed attack the tumors. The problem is that these cells have difficulty penetrating the aggressive tumours, allowing pancreatic ductal adenocarcinoma to evade destruction.
Recently, researchers have found that folinic acid, a common chemotherapy supplement, weakens cancer's defenses in mice. They discovered that folinic acid boosts the levels of two key anti-cancer immune molecules in pancreatic ductal adenocarcinoma: natural killer T (NKT) cells and type-I interferons. This results in a stronger immune response, slower tumour growth, and longer survival in mice.
Scientists further revealed that pancreatic ductal adenocarcinoma defends itself against immune cells by creating a nearly impenetrable barrier using two proteins—CXCR4 and CXCL12. However, when the team treated pancreatic ductal adenocarcinoma tumors with folinic acid, this shield showed vulnerabilities.
The increased levels of NKT cells and type-I interferons acted as markers, revealing paths through pancreatic ductal adenocarcinoma's defenses. This allowed immune cells that had been barred from entering the tumour to penetrate the barrier and begin attacking the cancer.
Reference: Li, J., Moresco, P., & Fearon, D. T. (2024). Intratumoral NKT cell accumulation promotes antitumor immunity in pancreatic cancer. Proceedings of the National Academy of Sciences, 121(30), 2403917121. https://doi.org/10.1073/pnas.2403917121.
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