It is worth noting the effects that autocrine IGF-II exerts exclusively via the IRA independently of the IGF1R, such as in regards to EphB4 acute protein level regulation in certain cancers such as malignant mesothelioma [14], making the IGF-II/IRA signal in these cancers a distinctive, non-redundant ligand–receptor loop with targetable value. Here, IGF2 is linked to malignant mesothelioma.