Anti-insulin-like growth factor strategies in breast cancer.
The insulin-like growth factors (IGF-I and -II) are potent mitogens and survival factors for both normal and malignant breast cells. These effects are mediated primarily through the IGF-I receptor (IGF-IR), which is significantly overexpressed and highly activated in breast tumors. The IGF-binding proteins are competitive inhibitors of IGF/IGF-IR interaction, limiting cellular proliferation and survival. Higher serum IGF-I levels or an increased ratio of IGF-I to IGF binding protein-3 is associated with an increased risk of developing breast cancer. Hence, interest in the IGF system as a potential target for the development of novel antineoplastic therapies has ensued. Several strategies to interrupt IGF-IR signaling are currently being evaluated for the treatment of breast cancer, including suppression of IGF production, reduction of functional IGF-IR levels, neutralization of IGF action, and inhibition of IGF-IR activation.
Jerome
Lori
L
Department of Oncology, McGill University, Montreal, Quebec, Canada.
Shiry
Laura
L
Leyland-Jones
Brian
B
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D017451:Receptors, Somatomedin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D017451:Receptors, Somatomedin