PIK3CA and cancer: Unbiased genetic and pharmacologic screens revealed three distinct classes of synthetic lethal targets that synergize with both MEK and KRASG12C inhibitors in KRAS-mutated cancer cells [112,127,128]: (i) individual RTKs or proximal RTK signaling components (including SHP2 and SOS1) whose inhibition can broadly inhibit RTK signaling, (ii) mTOR/PI3K survival signaling components, and (iii) regulators of cell cycle progression.