The type I IGF receptor as a target for breast cancer therapy.
The limitations of conventional systemic therapy for breast cancer have encouraged the development of novel therapeutic approaches. Trastuzumab, a humanized antibody directed against HER2, has entered the clinic as a successful therapy for patients with HER2 positive breast cancers demonstrating the therapeutic potential of anti-growth factor receptor strategies. Abundant experimental and epidemiological evidence has also suggested that the insulin-like growth factor (IGF) system is a treatment target in breast cancer. IGF receptor activation has important functions in malignant transformation, cell proliferation, protection from cell death, and metastasis of breast cancer cells. The requirement of ligand-receptor interaction to trigger the signaling cascade in IGF system has made several strategies plausible. These include lowering the circulating IGFs, neutralization of IGF action by IGF binding proteins, disruption of ligand binding to receptor by monoclonal antibodies, inhibition of IGF receptor tryosine kinase activity, and targeting of downstream signaling pathways. While the optimal anti-IGF strategy remains to be defined, the addition of IGF-targeting strategies alone or in combination with other modalities could provide a new avenue for breast cancer treatment.
Zhang
Xihong
X
University of Minnesota Cancer Center, MMC 806, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
Yee
Douglas
D