Interference of the IGF system as a strategy to inhibit breast cancer growth.
Experimental evidence suggests that human breast cancer cells can be regulated by the IGF-I and IGF-II present in the tumor stromal elements and/or by the endogenous tumor cell IGF-II in a paracrine or autocrine fashion. Thus, blockade of the receptor signalling pathway could lead to diminished tumor growth. Blockade of the type I IGF receptor by a monoclonal antibody (alpha IR3) has been used as a strategy to demonstrate the importance of the IGF pathway. Although alpha IR3 could not block serum-free growth of breast cancer cell lines, it could inhibit anchorage independent growth in most cell lines in the presence of serum. In vivo, alpha IR3 administered at the time of tumor cell inoculation could inhibit MDA-MB-231 tumor formation in athymic mice; however, inhibition of established tumors was not seen. Moreover, alpha IR3 could not inhibit tumor formation of the MCF-7 cell line in vivo. These results suggest that blockade of the type I IGF receptor can inhibit the growth of some breast cancer cells both in vitro and in vivo. Future anti-growth factor strategies include the combination of anti-IGF receptor antibodies with IGF neutralizing modalities, the dual blockade of growth factor receptors (epidermal growth factor receptor and type I IGF receptor), and combinations of steroid hormone antagonists and anti-growth factor treatments to maximize tumor inhibition.
Arteaga
C L
CL
Department of Medicine, Vanderbilt University, Nashville, TN 37232-5536.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002455:Cell Division / Q000502:physiology; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors; D013002:Somatomedins / Q000037:antagonists & inhibitors / Q000502:physiology*
D000911:Antibodies, Monoclonal; D013002:Somatomedins; D017526:Receptor, IGF Type 1