In addition and in line with similar studies performed with RAF1 shRNA in pancreatic cancer [7], bladder tumors [59], lung adenocarcinoma [17] and CRC [22], we demonstrated that a combination of RAF1 ablation and MEK inhibition greatly impairs cell proliferation in 3D spheroids from human CRC cell lines and CRC patient-derived organoids, confirming that combination therapies might be a strategy in CRC. Here, RAF1 is linked to familial pancreatic carcinoma.