This parallel increase in IGF2 transcription, coupled with defective cancer processing, generates the known high-molecular IGF-II pro-hormone variants [11], which are refractive to IGFBP-3 [49,50] (and SpI2-6/IGF2R) binding [50] but not to the IGF-II RTKs (IGF-IR and IRA) which are efficiently activated [11,50]. Here, IGF2 is linked to cancer.