Georgia Hatzivassiliou

TL;DR: It is demonstrated that ATP-competitive kinase inhibitors can have opposing functions as inhibitors or activators of signalling pathways, depending on the cellular context, which provides new insights into the therapeutic use of ATP- competitive RAF inhibitors.

TL;DR: It is shown that, owing to distinct mechanisms regulating MEK activation in KRAS- versus BRAF-driven tumours, different mechanisms of inhibition are required for optimal antitumour activity in each genotype.

TL;DR: This paper identified three highly distinct metabolic subtypes in pancreatic ductal adenocarcinoma (PDAC) using broad metabolite profiling, which corresponded to differences in cell sensitivity to inhibitors of glycolysis, glutamine metabolism, lipid synthesis, and redox balance.

TL;DR: The data suggest that tumors with acquired MEK inhibitor resistance remain dependent on the MAPK pathway and are therefore sensitive to inhibitors that act downstream of the mutated MEK target, and provide a rationale for cotargeting multiple nodes within theMAPK signaling cascade in K-ras mutant tumors to maximize therapeutic benefit for patients.

TL;DR: Combined inhibition of glycolysis and mTORC1 signaling disrupted metabolic reprogramming in tumor cells and inhibited their growth in vitro and in vivo, revealing novel combinatorial therapeutic strategies to realize the potential benefit from targeting the Warburg effect.