Abstract
Abstract IGF-1 receptor (IGF-1R) plays a key role in the development of numerous tumors. Blockade of IGF-1R axis using monoclonal antibodies constitutes an interesting approach to inhibit tumor growth. We have previously described h7C10 (also named MK-0646), a humanized anti-IGF-1R Mab, that exhibits a potent anti-tumor activity both in vitro and in vivo. It blocks IGF-1 and IGF-2 induced signaling and blocks in vivo tumor growth of IGF-IR expressing tumors. In this report, we examined the in vitro effects of this selective IGF-1R Mab in combination with a panel of chemotherapeutic agents. The effect of drugs and h7C10 on the growth of human breast cancer cell line MCF-7 was determined by 3H-thymidine incorporation in DNA. The combined effect of drugs and h7C10 on MCF-7 cell line was evaluated by the combination index (CI) analysis method described by Chou and Talalay. We showed that the combination of h7C10 with a panel of drugs namely, paclitaxel, docetaxel, doxorubicin and gemcitabine induced synergistic inhibitory effects on MCF-7 breast cancer cell proliferation in vitro. These findings demonstrated that h7C10 combined with established cancer therapeutics is highly effective against cancer cells that expressed IGF-1R and support clinical evaluation of h7C10 in combination with these drugs in the treatment of human cancers. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B131.
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