EGFR and colorectal carcinoma: The EGFR signaling activates PI3K, which activates the PI3K-AKT-mTOR pathway-involved combinations.76 Preclinical models have shown activation of both EGFR and PI3K signaling in BRAFV600E-mutant CRC cell lines.77 A phase Ib dose-finding study with a triple combination of encorafenib, cetuximab, and alpelisib (PI3K inhibitor) demonstrated longer PFS in BRAFV600E mCRC patients with amplified EGFR.78 Patients with mutations in the PI3K pathway were also responsive to the addition of alpelisib.