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Endothelial ALK1 Is a Therapeutic Target to Block Metastatic Dissemination of Breast Cancer.
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- Cunha, Sara I. (author)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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- Bocci, Matteo (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Experimentell onkologi,Forskargrupper vid Lunds universitet,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Experimental oncology,Lund University Research Groups
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- Lövrot, John (author)
- Karolinska Institutet
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- Roswall, Pernilla (author)
- Haller, B Kristian (author)
- Pearsall, R Scott (author)
- Mulivor, Aaron W (author)
- Kumar, Ravindra (author)
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- (creator_code:org_t)
- 2015
- 2015
- English.
- In: Cancer Research. - 1538-7445 .- 0008-5472. ; 75:12, s. 2445-2456
- Journal article (peer-reviewed)
Abstract
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- Exploration of new strategies for the prevention of breast cancer metastasis is justifiably at the center of clinical attention. In this study, we combined a computational biology approach with mechanism-based preclinical trials to identify inhibitors of activin-like receptor kinase (ALK) 1 as effective agents for blocking angiogenesis and metastasis in breast cancer. Pharmacologic targeting of ALK1 provided long-term therapeutic benefit in mouse models of mammary carcinoma, accompanied by strikingly reduced metastatic colonization as a monotherapy or part of combinations with chemotherapy. Gene-expression analysis of breast cancer specimens from a population-based nested case-control study encompassing 768 subjects defined endothelial expression of ALK1 as an independent and highly specific prognostic factor for metastatic manifestation, a finding that was corroborated in an independent clinical cohort. Overall, our results suggest that pharmacologic inhibition of endothelial ALK1 constitutes a tractable strategy for interfering with metastatic dissemination of breast cancer. Cancer Res; 75(12); 2445-56. ©2015 AACR.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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