Given that individual targeting of RAGE and its ligands have revealed sufficient inhibition of growth, spread and angiogenesis of tumours in multiple studies, the simultaneous targeting of the RAGE-ligand duo with RAGE-ligand antagonists should be strong enough to offer remarkable control over the “Achilles’ heel” of cancers, especially metastasis, therapy resistance, cancer resurgence and impaired patient prognosis [79]. This evidence concerns the gene AGER and cancer.