Customizing the Targeting of IGF-1 Receptor

Renato Baserga

Disclosures

Future Oncol. 2009;5(1):43-50. 

In This Article

IGF-IR & Combined Therapies

Targeting the IGF-IR, by a variety of approaches, has been found to be effective against xenotransplanted human tumors in combination with other anticancer therapeutic treatments, such as chemotherapy[4,46] or ionizing radiation.[47,48] This is not surprising since it is rare that single agents are effective in the therapy of human cancers. In the majority of cases, multiple agents have to be combined if one wishes to obtain a curative effect or a complete prevention of metastases. The efficacy of the IGF-IR in combined therapies illustrates another function of the IGF-IR, which is independent of its mitogenic action. The IGF-IR is known to send a strong antiapoptotic signal through three separate pathways.[49] Indeed, in cells of neuronal origin, IGFs have a modest mitogenic effect, but give a very strong survival signal.[50] In combined therapies, one usually hopes to have the additive effect of two agents, both inhibiting the proliferation of cancer cells. In the case of the IGF-IR, the situation is slightly different. One can exploit the antiapoptotic action of the IGF-IR by inducing cell death with another agent, and lessening cell resistance to injury by interfering with IGF-IR signaling. In this instance, we would be targeting both IRS-1 and IRS-2 signaling, instead of IRS-1 only - that is, IGF-IR signaling in general, rather than its mitogenic pathway(s) (see above). A minimal advantage of combined therapies would be the possibility of decreasing the toxicity of chemotherapeutic agents or of ionizing radiations.

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