Insulin-like growth factor II (IGF-II) (IGF-II)

Insulin-like growth factor II (IGF-II) is a 67-amino acid peptide hormone that serves as a critical mediator of fetal growth and development (UniProt P01344). Structurally related to insulin and IGF-I, it exerts its biological effects primarily through the Type 1 IGF receptor (IGF-1R) and the A-isoform of the insulin receptor (IR-A), promoting cell proliferation, survival, and differentiation (PubMed: 33050575). While its expression is tightly regulated by genomic imprinting—typically expressed only from the paternal allele—loss of this imprinting leads to IGF-II overexpression, a hallmark of growth disorders like Beckwith-Wiedemann syndrome and various malignancies, including Wilms' tumor and colorectal cancer (PubMed: 18248917). In the oncogenic context, IGF-II acts as an autocrine and paracrine growth factor that drives tumor progression and confers resistance to standard therapies (PubMed: 25893001). Therapeutic interventions, such as the monoclonal antibodies dusigitumab (MEDI-573) and xentuzumab (BI 836845), aim to neutralize circulating IGF-II to inhibit these mitogenic pathways (PubMed: 25893001, 33050575). However, drug development faces challenges due to the potential for metabolic side effects, such as altered glucose homeostasis, arising from the structural similarity between IGF-II and insulin (PubMed: 25893001).

Other names

IGF2Somatomedin-APreptinInsulin-like growth factor 2

Neutralization and sequestration of the IGF-II ligand to prevent its binding and activation of the IGF-1R and IR-A signaling pathways.