# pancreatic ductal adenocarcinoma

Microsoft Research introduces Quine, a research system combining a world model of biology trained jointly across modalities including sequence, structure, function, cellular state, and imaging with a harness connecting scientific tools, literature, the wet lab, and researchers; with the Broad Institute it used the system in pancreatic ductal adenocarcinoma (PDAC) to predict and prioritize thousands of compounds by their potential to shift tumor cells between therapeutically relevant states, wet-lab assays showed Quine's highest-ranked compounds produced the largest intended shifts, the whole process from narrowing the search space to prioritizing a handful of candidates took just one weekend, and the experiments also bore out the model's prediction of a distinct third phenotype.

Microsoft Research introduces Quine, a research system combining a world model of biology trained jointly across modalities including sequence, structure, function, cellular state, and imaging with a harness connecting scientific tools, literature, the wet lab, and researchers; with the Broad Institute it used the system in pancreatic ductal adenocarcinoma (PDAC) to predict and prioritize thousands of compounds by their potential to shift tumor cells between therapeutically relevant states, wet-lab assays showed Quine's highest-ranked compounds produced the largest intended shifts, the whole process from narrowing the search space to prioritizing a handful of candidates took just one weekend, and the experiments also bore out the model's prediction of a distinct third phenotype.

This review systematically examines the molecular mechanisms of perineural invasion (PNI) in pancreatic ductal adenocarcinoma, proposes a unified four-stage model spanning mutual chemotaxis between tumors and nerves, adhesion and invasion at the tumor-nerve interface, extracellular matrix remodeling, and neural plasticity alterations, defines the perineural invasion microenvironment as a neuro-immune privileged sanctuary, and summarizes therapeutic strategies targeting the neuro-immune-tumor axis, ongoing clinical trials, and the applications of multi-omics and artificial intelligence in PNI diagnosis, mechanistic discovery, and therapeutic optimization.

This review systematically examines the molecular mechanisms of perineural invasion (PNI) in pancreatic ductal adenocarcinoma, proposes a unified four-stage model spanning mutual chemotaxis between tumors and nerves, adhesion and invasion at the tumor-nerve interface, extracellular matrix remodeling, and neural plasticity alterations, defines the perineural invasion microenvironment as a neuro-immune privileged sanctuary, and summarizes therapeutic strategies targeting the neuro-immune-tumor axis, ongoing clinical trials, and the applications of multi-omics and artificial intelligence in PNI diagnosis, mechanistic discovery, and therapeutic optimization.

In 203 patients with pancreatic ductal adenocarcinoma who received neoadjuvant therapy and curative-intent resection and were restricted to minor pathologic response, an AI-enabled pipeline segmented cancer and stroma from routine H&E whole-slide images and quantified spatial composition and configuration, finding that a fragmented, interface-rich tumor-stroma ecology was independently associated with shorter disease-free survival; two spatial risk models (cancer mean shape index plus stromal shape index variability, adjusted HR 1.71, P = 0.003; mean stromal patch area plus edge density, adjusted HR 2.19, P = 0.

In 203 patients with pancreatic ductal adenocarcinoma who received neoadjuvant therapy and curative-intent resection and were restricted to minor pathologic response, an AI-enabled pipeline segmented cancer and stroma from routine H&E whole-slide images and quantified spatial composition and configuration, finding that a fragmented, interface-rich tumor-stroma ecology was independently associated with shorter disease-free survival; two spatial risk models (cancer mean shape index plus stromal shape index variability, adjusted HR 1.71, P = 0.003; mean stromal patch area plus edge density, adjusted HR 2.19, P = 0.