JCI Induced clustering of SHP2-depleted tumor cells in vascular islands restores sensitivity to MEK/ERK inhibition

JCI Induced clustering of SHP2-depleted tumor cells in vascular islands restores sensitivity to MEK/ERK inhibition

Allosteric inhibitors of the tyrosine phosphatase Src homology 2 domain–containing protein tyrosine phosphatase 2 (SHP2) hold therapeutic promise in cancers with overactive RAS/ERK signaling, but adaptive resistance to SHP2 inhibitors may limit benefits. Here, we utilized tumor cells that proliferate similarly with or without endogenous SHP2 to explore means to overcome this growth independence from SHP2. We found that SHP2 depletion profoundly …