Intermolecular biparatopic trapping of ErbB2 prevents compensatory activation of PI3K/AKT via RAS–p110 crosstalk

Abstract

Targeted therapy of ErbB2-dependent tumours often provokes an adaptive response leading to reactivation of the PI3K/AKT pathway. Here the authors identify an ErbB3-independent compensatory mechanism comprising Ras/PI3K activation directly by ErbB2, and develop biparatopic panErbB inhibitors to block this mode of resistance.