RIOK1 and cancer: However, the strongest rationale for selecting RIOK1 for further investigation had to do with the limited efficacy and intrinsic resistance seen in phase I/II clinical trials of patients treated with Sotorasib and Adagrasib, (KRASG12C selective inhibitors [49,50]) and the fact that knockdown of RIOK1 strongly impairs proliferation and invasiveness in conventional and 3D culture systems in RAS-mutant cancer cells [24].