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. 2015 Feb 2;6:12. doi: 10.3389/fendo.2015.00012

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Copyright © 2015 Salisbury and Tomblin.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Mechanism of action of MEDI-573, anti-IGF1R antibodies, and OSI-906 in cancer cells and tumor angiogenesis. IGF2 binding to insulin receptor subtype A (IR-A) and IGF1 binding to IGF1R in cancer cells and tumor blood vessels promotes cancer cell survival and proliferation as well as tumor angiogenesis. MEDI-573 is a human antibody that neutralizes IGF2 and IGF1 and thus inhibits the cancer effects of both IGF ligands. Anti-IGF1R antibodies inhibit IGF1 signaling through IGF1R, but not IGF2 signaling mediated by IR-A. OSI-906 is a small molecule inhibitor that inhibits IGF1R and IR autophosphorylation and therefore IGF1 and IGF2 cancer effects.