Cancer esearch apeutics , Targets , and Chemical Biology Is an Essential Factor and Therapeutic Target R Metastatic Ovarian Cancer

nloaded receptor tyrosine kinase AXL is thought to play a role in metastasis; however, the therapeutic efficacy of L-targeting agent remains largely untested in metastatic disease. In this study, we defined AXL as a eutic target for metastatic ovarian cancer. AXL is primarily expressed in metastases and advanced-stage ovarian tumors but not in normal ovarian epithelium. Genetic inhibition of AXL in human metastatic n tumor cells is sufficient to prevent the initiation of metastatic disease in vivo. Mechanistically, inhiof AXL signaling in animals with metastatic disease results in decreased invasion and matrix metallonase activity. Most importantly, soluble human AXL receptors that imposed a specific blockade of the AXL pathway had a profound inhibitory effect on progression of established metastatic ovarian cancer t normal tissue toxicity. These results offer the first genetic validation of GAS6/AXL targeting as an ve 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. Cancer Res; 70(19); 7570–9. ©2010 AACR.