Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The receptor tyrosine kinase AXL is thought to play a role in metastasis; however, the therapeutic efficacy of an AXL-targeting agent remains largely untested in metastatic disease. In this study, we defined AXL as a therapeutic target for metastatic ovarian cancer. AXL is primarily expressed in metastases and advanced-stage human ovarian tumors but not in normal ovarian epithelium. Genetic inhibition of AXL in human metastatic ovarian tumor cells is sufficient to prevent the initiation of metastatic disease in vivo. Mechanistically, inhibition of AXL signaling in animals with metastatic disease results in decreased invasion and matrix metalloproteinase activity. Most importantly, soluble human AXL receptors that imposed a specific blockade of the GAS6/AXL pathway had a profound inhibitory effect on progression of established metastatic ovarian cancer without normal tissue toxicity. These results offer the first genetic validation of GAS6/AXL targeting as an effective strategy for inhibition of metastatic tumor progression in vivo. Furthermore, this study defines the soluble AXL receptor as a therapeutic candidate agent for treatment of metastatic ovarian cancer, for which current therapies are ineffective.

Original publication

DOI

10.1158/0008-5472.CAN-10-1267

Type

Journal article

Journal

Cancer Res

Publication Date

01/10/2010

Volume

70

Pages

7570 - 7579

Keywords

Adenoviridae, Animals, Cell Line, Tumor, Female, Humans, Intercellular Signaling Peptides and Proteins, Mice, Mice, Nude, Neoplasm Metastasis, Ovarian Neoplasms, Plasmids, Proto-Oncogene Proteins, RNA, Small Interfering, Receptor Protein-Tyrosine Kinases, Signal Transduction, Xenograft Model Antitumor Assays