The secret origins and surprising fates of pancreas tumors

Pancreatic ductal adenocarcinoma (PDA) is especially deadly due to its recalcitrance to current therapies. One of the unique qualities of PDA that may contribute to this resistance is a striking plasticity of differentiation states starting at tumor formation and continuing throughout tumor progression, including metastasis. Here we explore the earliest steps of tumor formation and neoplastic progression and how this results in a fascinating cellular heterogeneity that is likely critical for tumor survival and progression. We hypothesize that reinforcing differentiation pathways run awry or targeting morphologically and molecularly distinct tumor stem-like cells may hold promise for future treatments of this deadly disease.