Insulin-like growth factor-I receptor signaling and resistance in breast cancer

Abstract

Insulin-like growth factor-I receptor (IGF-IR) signaling is involved in many fundamental adverse aspects of cancer cell biology, such as proliferation, cell survival and migration. Its anti-apoptotic properties have implicated the receptor in mediating decreased sensitivity to chemotherapeutic drugs and radiation treatment; however, data are emerging that also indicates a role for IGF-IR signaling in resistance, not only to antihormones but also to antigrowth factor strategies such as agents that target the erb family of receptors. As such, IGF-IR is clearly an attractive therapeutic target for the treatment of cancer, including breast cancer, where there is evidence of clinical prominence of the IGF-IR pathway and, as such, numerous strategies are currently in development to inhibit IGF-IR signaling. This review focuses on the ability of the IGF-IR to contribute to resistance mechanisms that support breast cancer cell growth in the presence of antihormones and antigrowth factors and discusses methods to maximize antitumor effects by combination regimens cotargeting the IGF-IR that may delay, or even prevent, progression to the resistant phenotype.

Keywords::

• AG1024
• breast cancer
• epidermal growth factor receptor
• gefitinib
• Insulin-like growth factor-I receptor
• HER-2
• resistance