Select Stabilization of a Tumor-Suppressive PP2A Heterotrimer.

In cancer, suppression of protein phosphatases, such as protein phosphatase 2A (PP2A), that normally counteract kinases, contributes to aberrant signaling. Leonard et al. recently demonstrated that a novel small-molecule activator of PP2A, DT-061, selectively stabilizes a specific PP2A holoenzyme responsible for dephosphorylating critical oncogenic targets, including MYC. The 3.6-Å cryo-electron microscopy map of the heterotrimer assembly provides insight into the druggable structure of PP2A, guiding future phosphatase therapeutics.

Deconstructing Pancreatic Adenocarcinoma by Targeting the Conductor, MYC.

In this issue of Cancer Discovery, Sodir and colleagues employ a pancreatic ductal adenocarcinoma mouse model with mutant KRAS and inducible MYC to demonstrate that MYC acts as a reversible driver of malignant tumor progression. Abrogation of MYC triggers rapid regression and disassembly of the ensemble tumor through both cancer cell-intrinsic and cancer cell-extrinsic mechanisms, providing a compelling rationale for therapeutic targeting of MYC.See related article by Sodir et al., p. 588.