Fig 1
From: Molecular alterations and targeted therapy in pancreatic ductal adenocarcinoma
ERBB family comprises four receptor tyrosine kinases including the epidermal growth factor receptor (EGFR). Activation of EGFR recruits RAS guanine nucleotide exchange factors (GEFs) such as son-of-sevenless (SOS). GEFs and GTPase activating proteins (GAPs) switch RAS between the GTP-bound and GDP-bound states. The constitutive GDP-bound state activates multiple downstream molecules in PDAC. Gene fusions such as NRG1 fusions can also initiate PDAC via ectopic ERBB receptor signalling pathway. IGF-1R has crosstalk with EGFR and produces tumour resistance to EGFR inhibitors. Various inhibitors could inhibit RAS signalling pathway molecules by targeting corresponding molecules such as EGFR, MEK, PI3K