IGF2 and cholangiocarcinoma: In cholangiocarcinomas treated with EGFR inhibitors, a positive loop between CAF-produced IGF2 and IGF1R expressed by tumor cells was responsible for resistance to the EGFR TKI erlotinib; in line, a combined regimen of EGFR and IGF1R inhibitors overcame resistance in cholangiocarcinoma xenografts and reduced their stromal content [74].