Selective inhibition of SCLC growth by the A12 anti-IGF-1R monoclonal antibody correlates with inhibition of Akt.

Activation of the insulin-like growth factor-1 receptor (IGF-1R) by IGF-1 and IGF-2 plays a prominent role in the growth and survival of small cell lung cancer (SCLC) by potently activating the PI3K-Akt signal transduction pathway, which is also an important factor in the resistance of SCLC to chemotherapy. A12 is a fully human monoclonal antibody directed against the human IGF-1R that does not cross-react with the insulin receptor. In this study we have utilized A12 to determine the effects of selective antibody-mediated blockade of the IGF-1R on SCLC cell lines.