Cited by 234Ovarian cancer diagnosis and treatmentCancer Cells and MetastasisCancer Mechanisms and Therapy

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AXL Is an Essential Factor and Therapeutic Target for Metastatic Ovarian Cancer

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Rankin, Erinn B., Fuh, Katherine C., Taylor, Tiffany E., Krieg, Adam J., Musser, Margaret, Yuan, Jenny, Wei, Kevin, Kuo, Calvin J., Longacre, Teri A., Giaccia, Amato J.·2010·Cancer Research

DOI 10.1158/0008-5472.can-10-1267PMC PMC3408227

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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. Cancer Res; 70(19); 7570–9. ©2010 AACR.

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RETRACTED ARTICLE: Soluble Axl Is Generated by ADAM10-Dependent Cleavage and Associates with Gas6 in Mouse Serum
Budagian, V., Bulanova, E., Orinska, Z., Duitman, E. H., Brandt, K., Ludwig, A., Hartmann, D., Lemke, G., Säftig, P., & Bulfone‐Paus, S. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.21.9324-9339.2005 · Cited by 84
Retracted
New functions for the matrix metalloproteinases in cancer progression
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The Origin and Pathogenesis of Epithelial Ovarian Cancer: A Proposed Unifying Theory
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Tumor Self-Seeding by Circulating Cancer Cells
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axl, a transforming gene isolated from primary human myeloid leukemia cells, encodes a novel receptor tyrosine kinase.
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Authors: Rankin, E. B., Fuh, K. C., Taylor, T. E., Krieg, A. J., Musser, M., Yuan, J., Wei, K., Kuo, C. J., Longacre, T. A., & Giaccia, A. J.
Affiliations: University of Illinois Urbana-Champaign (US)
Corresponding author: Giaccia, Amato J.
ORCID: Rankin, Erinn B.
Fuh, Katherine C.
Taylor, Tiffany E.
Krieg, Adam J.
Wei, Kevin
Kuo, Calvin J.
Longacre, Teri A.
Giaccia, Amato J.
Venue: Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2010-09-29
Volume: 70
Issue: 19
Pages: 7570-7579
ISSN: 0008-5472 (ISSN-L)
1538-7445
DOI: 10.1158/0008-5472.can-10-1267
PMC: PMC3408227
OpenAlex: W2132286757
Cited by: 229
References: 49
Citations by year: 2026: 5 · 2025: 10 · 2024: 16 · 2023: 14 · 2022: 16 · 2021: 18 · 2020: 13 · 2019: 14 · 2018: 18 · 2017: 17 · 2016: 25 · 2015: 20 · 2014: 14 · 2013: 16 · 2012: 6
FWCI: 11.00
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Cancer Research (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (CA116685, P01CA067166, T32CA009151, T32CA09151, F32CA124082, CA 67166, R01CA116685, T32CA009302)
National Institute of Diabetes and Digestive and Kidney Diseases (U24DK085532, U01DK085527, U01DK085532)
Topics: Health Sciences › Medicine › Oncology › Ovarian cancer diagnosis and treatment
Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Mechanisms and Therapy
Keywords: AXL receptor tyrosine kinase, metastatic ovarian cancer, therapeutic target, tumor invasion, matrix metalloproteinase activity, metastasis suppression
MeSH terms: Axl Receptor Tyrosine Kinase, Growth Arrest-Specific Protein 6, Adenoviridae, Animals, Female, Humans, Mice, Nude, Neoplasm Metastasis, Ovarian Neoplasms, Plasmids, Proto-Oncogene Proteins, Signal Transduction, Receptor Protein-Tyrosine Kinases, Xenograft Model Antitumor Assays, RNA, Small Interfering, Intercellular Signaling Peptides and Proteins, Cell Line, Tumor, Mice

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AXL Is an Essential Factor and Therapeutic Target for Metastatic Ovarian Cancer

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