AXL is an essential factor and therapeutic target for metastatic ovarian cancer

Erinn B. Rankin, Katherine C. Fuh, Tiffany E. Taylor, Adam Krieg, Margaret Musser, Jenny Yuan, Kevin Wei, Calvin J. Kuo, Teri A. Longacre, Amato J. Giaccia

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

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 languageEnglish (US)
Pages (from-to)7570-7579
Number of pages10
JournalCancer Research
Volume70
Issue number19
DOIs
StatePublished - Oct 1 2010
Externally publishedYes

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Ovarian Neoplasms
Neoplasm Metastasis
Neoplasms
Receptor Protein-Tyrosine Kinases
Therapeutics
Matrix Metalloproteinases
Epithelium

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Rankin, E. B., Fuh, K. C., Taylor, T. E., Krieg, A., Musser, M., Yuan, J., ... Giaccia, A. J. (2010). AXL is an essential factor and therapeutic target for metastatic ovarian cancer. Cancer Research, 70(19), 7570-7579. https://doi.org/10.1158/0008-5472.CAN-10-1267

AXL is an essential factor and therapeutic target for metastatic ovarian cancer. / Rankin, Erinn B.; Fuh, Katherine C.; Taylor, Tiffany E.; Krieg, Adam; Musser, Margaret; Yuan, Jenny; Wei, Kevin; Kuo, Calvin J.; Longacre, Teri A.; Giaccia, Amato J.

In: Cancer Research, Vol. 70, No. 19, 01.10.2010, p. 7570-7579.

Research output: Contribution to journalArticle

Rankin, EB, Fuh, KC, Taylor, TE, Krieg, A, Musser, M, Yuan, J, Wei, K, Kuo, CJ, Longacre, TA & Giaccia, AJ 2010, 'AXL is an essential factor and therapeutic target for metastatic ovarian cancer', Cancer Research, vol. 70, no. 19, pp. 7570-7579. https://doi.org/10.1158/0008-5472.CAN-10-1267
Rankin, Erinn B. ; Fuh, Katherine C. ; Taylor, Tiffany E. ; Krieg, Adam ; Musser, Margaret ; Yuan, Jenny ; Wei, Kevin ; Kuo, Calvin J. ; Longacre, Teri A. ; Giaccia, Amato J. / AXL is an essential factor and therapeutic target for metastatic ovarian cancer. In: Cancer Research. 2010 ; Vol. 70, No. 19. pp. 7570-7579.
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