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The oft-repeated statistics are dismal: pancreatic ductal adenocarcinoma (PDA) has only a 6% 5-year survival rate that has not changed significantly in 30 years and the vast majority of PDA patients perish within 6 months of diagnosis. Several possible reasons contribute to these grim results. PDA is difficult to detect, it is recalcitrant to most targeted treatments and conventional therapies only have a modest effect on survival. Compared with other cancers, PDA was revealed to be remarkably genetically homogenous with 95% or more of PDA harbouring oncogenic mutations in the Kras gene,1 generating hope that finding effective ways of interrupting Kras signalling would increase survival for PDA patients. However, Kras-targeted therapies have proven elusive thus far, leaving its downstream effectors as the most obvious potential targets.
The true genetic heterogeneity of PDA has just begun to be appreciated2 ,3 within a background of the almost universal presence of Kras mutation and the statistically predictable identities of many of the subsequent tumour suppressor mutations that propel its progression and metastasis. Of course, …