Ductal pancreatic cancer interception by FGFR2 abrogation.

Unlabelled: Activating KRAS mutations are a key feature of pancreatic ductal adenocarcinoma (PDA) and drive tumor initiation and progression. However, mutant KRAS by itself is weakly oncogenic. The pathways that cooperate with mutant KRAS to induce tumorigenesis are less-defined.

MARK2/MARK3 Kinases Are Catalytic Codependencies of YAP/TAZ in Human Cancer.

The Hippo signaling pathway is commonly dysregulated in human cancer, which leads to a powerful tumor dependency on the YAP/TAZ transcriptional coactivators. In this study, we used paralog cotargeting CRISPR screens to identify kinases MARK2/3 as absolute catalytic requirements for YAP/TAZ function in diverse carcinoma and sarcoma contexts. Underlying this observation is the direct MARK2/3-dependent phosphorylation of NF2 and YAP/TAZ, which effectively reverses the tumor suppressive activity of the Hippo module kinases LATS1/2.

Locally advanced pancreatic cancer: Is surgical palliation associated with improved clinical outcome relative to medical palliation?

Background: The value of palliative surgery in pancreatic cancer is not well-defined.

Methods: We queried the National Cancer Database for patients undergoing curative-intent resection, palliative surgery or medical palliation for clinical stage cT4N0-2M0 pancreatic cancer. Cohorts were 1:1:1 propensity-score-matched for comorbidities and stage.

A mucus production programme promotes classical pancreatic ductal adenocarcinoma.

Objective: The optimal therapeutic response in cancer patients is highly dependent upon the differentiation state of their tumours. Pancreatic ductal adenocarcinoma (PDA) is a lethal cancer that harbours distinct phenotypic subtypes with preferential sensitivities to standard therapies. This study aimed to investigate intratumour heterogeneity and plasticity of cancer cell states in PDA in order to reveal cell state-specific regulators.

Engrailed-1 Promotes Pancreatic Cancer Metastasis.

Engrailed-1 (EN1) is a critical homeodomain transcription factor (TF) required for neuronal survival, and EN1 expression has been shown to promote aggressive forms of triple negative breast cancer. Here, it is reported that EN1 is aberrantly expressed in a subset of pancreatic ductal adenocarcinoma (PDA) patients with poor outcomes. EN1 predominantly repressed its target genes through direct binding to gene enhancers and promoters, implicating roles in the activation of MAPK pathways and the acquisition of mesenchymal cell properties.