Although EphB4 expression has been found upregulated in response to IGF-I in vitro [5], the IGF-II autocrine loop has been shown to be a hallmark for a variety of cancers in vivo where its systemic effects are responsible for the cancer-associated syndrome previously known as non-insulin-dependent-hypoglycemia (NIDH) later referred as to IGF2omas [16]. The gene discussed is EPHB4; the disease is cancer.