Figure 7.

Ras signaling pathways and synthetic lethal interactions. Receptor tyrosine kinases (RTK) activate RAS and PI3K/AKT/mTOR pathways. RAS in turn activates RAF/MEK/ERK, PI3K/AKT/mTOR, and RalGEF/Ral pathways and crosstalks with RTK, WNT, c-Jun N-terminal kinases (JNK), reactive oxidative species (ROS), STAT3, and tumor necrosis factor α (TNFα)/NFκB pathways. Several key nodes in those signaling networks, such as TBK1, PLK1, CDK4, SYK, and WT1 (colored tan), have been reported to have synthetic lethal interactions with oncogenic RAS. In contrast, activation of p53 and JNK may lead to apoptosis. Arrow indicates activation, and the line terminating with a black circle indicates suppression.