A Sampling of Highlights from the Literature: Article Recommendations from Our Deputy and Senior Editors

Mutated, activated KRAS is a common feature of pancreatic ductal adenocarcinoma (PDAC). Inhibitors of the downstream MEK and CDK4/6 pathways suppress PDAC growth by inducing cellular senescence and production of chemokines, cytokines, and matrix metalloproteinases. This triggers vasculature remodeling of the PDAC tumors and subsequent NF-κB– and VEGFR-driven tumor infiltration by CD8⁺ T cells. MEK and CDK4/6 inhibitors lead to exhaustion of the recruited T cells, which are rescued by PD-1 blockade. Inducing senescence with immune checkpoint blockade may improve outcomes.

Ruscetti M, …, Lowe SW. Cell 2020 Apr 16;181:424–41.e21.

Radiation induces genomic DNA (gDNA) fragmentation but little cytosolic DNA sensing with IFN-I production. Radiation also induces mitochondrial permeabilization, and the mitochondrial DNA (mtDNA) activates caspase-9, leading to intrinsic apoptosis. By disrupting caspase-9, apoptosis is inhibited and the cytosolic mtDNA activates the STING pathway...