A groundbreaking triple-drug therapy has shown remarkable success in eliminating pancreatic cancer tumors and preventing their recurrence in several mouse models. By simultaneously blocking three important growth paths
The nontoxic treatment represents a promising new strategy to overcome the disease’s notorious treatment resistance.
Targeting the cancer survivor network
The study, published in PNAS, addresses a key weakness of current treatments: the ability of cancer to find “another door” to survival when one pathway is blocked. Lead author Carmen Guerra and her team found that when key growth drivers like KRAS (mutated in almost all pancreatic cancers) are inhibited, a backup protein called STAT3 becomes highly active. The new therapy strategically combines drugs to block KRAS, a related signaling pathway, and STAT3 simultaneously.
The three-drug cocktail and stunning results
The therapy uses:
- Afatinib: An FDA-approved drug for lung cancer.
- Darakhonrasib: A drug currently in clinical trials.
- A novel STAT3 inhibitor.
The combination was tested in three rigorous mouse models – including one with human tumor samples – and completely eliminated pancreatic tumors. “You couldn’t even see where the tumor was. The pancreas was completely healthy,” Guerra reported. Crucially, the cancer did not recur for at least 200 days after treatment and the therapy did not show any debilitating side effects in the mice.
Why this breakthrough is important
Pancreatic ductal adenocarcinoma, the most common form, has a five-year survival rate of only 13%, decreasing to 1% in later stages. Standard chemotherapy attacks all rapidly dividing cells, causing serious side effects and causing tumors to quickly develop resistance. This targeted approach aims to outmaneuver the cancer’s ability to adapt by simultaneously shutting down its primary and emergency survival routes.
The way forward: Cautious optimism
While the mouse results are extraordinary, the researchers acknowledge the leap to human patients. Some drugs in the cocktail, such as afatinib, are known to cause side effects (skin and gastrointestinal problems) in people. The team is now working on developing better-tolerated drugs that target the same signaling pathways. To ensure broad effectiveness, further tests in mouse models with various genetic mutations are also planned.
Supportive care and wellness for patients:
Sources:
This report is based on the peer-reviewed study in Proceedings of the National Academy of Sciences (PNAS).
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