The DOI matches its Crossref record; 47 of the 49 references it cites were found in a registry or an index.
AXL Is an Essential Factor and Therapeutic Target for Metastatic Ovarian Cancer
Open accessPublished version of a preprint
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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“A growing body of literature supports an essential role for AXL in promoting metastasis within many tumor types, including breast (81), ovarian (82), and lung (83).”
From Hypoxic control of metastasis (2016) · cites this paper as [82]
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1 retracted
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RetractedNew functions for the matrix metalloproteinases in cancer progression
Egeblad, M., & Werb, Z. (2002) · Nature Reviews Cancer · doi:10.1038/nrc745 · Cited by 6,108
Matrix Metalloproteinase Inhibitors and Cancer—Trials and Tribulations
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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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Homeostatic Regulation of the Immune System by Receptor Tyrosine Kinases of the Tyro 3 Family
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Rankin, E. B., & Giaccia, A. J. (2016) · Science · doi:10.1126/science.aaf4405 · Cited by 1,340
Self-citationBiomarkers for the early diagnosis of hepatocellular carcinoma
Tsuchiya, N. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i37.10573 · Cited by 571
Zhu, C., Wei, Y., & Wei, X. (2019) · Molecular Cancer · doi:10.1186/s12943-019-1090-3 · Cited by 507
Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma
Zhou, L., Liu, X.-D., Sun, M., Zhang, X., German, P., Bai, S., Ding, Z., Tannir, N. M., Wood, C. G., Matin, S. F., et al. (2015) · Oncogene · doi:10.1038/onc.2015.343 · Cited by 400
Self-citationAsiedu, M. K., Beauchamp‐Perez, F., Ingle, J. N., Behrens, M. D., Radisky, D. C., & Knutson, K. L. (2013) · Oncogene · doi:10.1038/onc.2013.57 · Cited by 302
Metadata
- 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
- Venue
- Cancer Research
- Published
- 2010-09-29
- Volume
- 70
- Issue
- 19
- Pages
- 7570-7579
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- 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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