Koji Miyabayashi

TL;DR: A pancreatic cancer patient-derived organoid (PDO) library is generated that recapitulates the mutational spectrum and transcriptional subtypes of primary Pancreatic cancer and proposes that combined molecular and therapeutic profiling of PDOs may predict clinical response and enable prospective therapeutic selection.

TL;DR: This study used an organoid culture system to investigate how transcription and the enhancer landscape become altered during discrete stages of disease progression in a PDA mouse model, and revealed that the metastatic transition is accompanied by massive and recurrent alterations in enhancer activity.

TL;DR: It is shown that expression of the transcription factor TP63 (∆Np63) is sufficient to install and sustain the enhancer landscape and transcriptional signature of the squamous lineage in human PDA cells, and that TP63-driven enhancer reprogramming promotes aggressive tumor phenotypes.

TL;DR: A xenotransplantation model of PDAC is presented in which neoplasms originate from patient-derived organoids injected directly into murine pancreatic ducts and a suite of RAS-regulated secreted and membrane bound proteins are identified which may represent potential candidates for therapeutic intervention in PDAC patients.

TL;DR: These findings reveal enhanced tissue inflammation as a consequence of squamous trans-differentiation in pancreatic cancer, thus highlighting an instructive role of tumor cell lineage in reprogramming the stromal microenvironment.