A shifting adversary: control of pancreatic cancer transcriptomic subtypes

Abstract

Cellular plasticity, the dynamic ability of cells to adopt distinct transcriptional states, plays a well-known role in the pancreas during the initiation of pancreatic ductal adenocarcinoma (PDA), the most common form of pancreatic cancer. It is now becoming clear that plasticity also plays an important role after the emergence of PDA. PDA is composed of two major transcriptional subtypes, classical and basal-like, with important biological differences. Recent work has indicated that individual tumors can be comprised of cells of each subtype, and that tumor subtype can change during the evolution of a tumor. This suggests that PDA cells can transit between transcriptional states, with important implications for disease progression. This review discusses what is currently known about inter-subtype plasticity and how this process is controlled.

Keywords

Pancreatic ductal adenocarcinoma / transcriptional subtypes / classical / basal-like / squamous / quasi-mesenchymal / cellular plasticity / transcription factors / tumor microenvironment

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