Pancreatic carcinoma is a tumor with an extremely poor prognosis for which effective treatments have not yet been found.
In a new study from the Technical University of Munich, researchers discovered a way of making pancreatic tumors treatable with immunotherapy methods using a targeted combination of two cancer drugs.
The researchers believe that the promising combined approach could also prove effective with other cancer types.
Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer. The disease is almost always fatal, with a 10-year survival rate of around 1%.
The prognosis is especially poor for a subgroup of these tumors known as mesenchymal PDAC subtype, where even the strongest combination chemotherapies do not improve the poor clinical outcomes.
In the study, the team found drug trametinib showed early promise with cancers that activate the RAF-MEK-ERK signaling pathway.
Because pancreatic cancers of the mesenchymal subtype show the highest activation of this pathway, it appeared likely that a drug that inhibits this pathway could offer therapeutic benefits.
Experiments showed, however, that treatments with trametinib alone were insufficient.
The researchers, therefore, conducted high-throughput screening of 418 drugs and discovered that nintedanib, a drug already approved for lung fibrosis treatment, stimulated T-cells infiltration when used in combination with trametinib.
The combination of the two drugs led to cell cycle arrest and the death of cancerous cells. They also changed the microenvironment of the tumor.
Next, the researchers found immunotherapy improved the effect of the combination treatment with trametinib and nintedanib.
The triple treatment strongly improved the response of the tumor, leading to a clear survival advantage of the highly aggressive mesenchymal PDAC subtype.
The results represent an important first step toward targeted treatment of PDAC, for which there are currently no efficient therapeutic options.
The researchers believe that the combination treatment may also have the potential to create anti-tumor immunity with other cancer types, resulting in improved therapeutic outcomes.
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The study is published in Nature Cancer and was conducted by Dieter Saur et al.
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