03 September 2019

Pancreatic ductal carcinoma (PDAC), although the most common malignancy of the pancreas, is a very aggressive and difficult malignancy to treat. With most pancreatic cancers being advanced when diagnosed, survival rates are extremely low. The search for information regarding the mechanisms driving these malignancies is therefore urgent.

A research team at Hokkaido University conducted tests which showed that two well-known pancreatic driver mutations (KRAS and TP53 mutations) both activate a specific signalling pathway (the ARF6–AMAP1 pathway) that promotes tumour malignancy through mechanisms such as immune evasion. Activation of the ARF6-AMAP1 pathway increases tumour cell surface expression of PD-L1, which helps the cell to hide from the immune system. TP53 mutations in addition stimulated the mevalonate pathway, which is associated with cancer invasiveness.

These results provided insight into the molecular pathways by which cells develop malignant features and evade immune detection, as well as suggesting potential druggable targets for immunotherapies.

Although the ARF6–AMAP1 pathway seems to be crucially involved in the malignancy of PDAC, further studies will be required to uncover the precise mechanisms and targets involved.

Reference: FirstWorld Pharma