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Endothelial ALK1 Is a Therapeutic Target to Block Metastatic Dissemination of Breast Cancer.

Cunha, Sara I; Bocci, Matteo LU ; Lövrot, John; Eleftheriou, Nikolas LU ; Roswall, Pernilla; Cordero, Eugenia LU ; Lindström, Linda; Bartoschek, Michael LU ; Haller, B Kristian and Pearsall, R Scott, et al. (2015) In Cancer Research 75(12). p.2445-2456
Abstract
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... (More)
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. (Less)
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published
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Cancer Research
volume
75
issue
12
pages
2445 - 2456
publisher
American Association for Cancer Research Inc.
external identifiers
  • pmid:26077471
  • wos:000357334400006
  • scopus:84941736038
ISSN
1538-7445
DOI
10.1158/0008-5472.CAN-14-3706
language
English
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yes
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deefdc5f-3e9c-4f9b-ab10-9647ee566a54 (old id 7485927)
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http://www.ncbi.nlm.nih.gov/pubmed/26077471?dopt=Abstract
date added to LUP
2015-07-08 16:31:06
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2017-10-22 03:20:20
@article{deefdc5f-3e9c-4f9b-ab10-9647ee566a54,
  abstract     = {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.},
  author       = {Cunha, Sara I and Bocci, Matteo and Lövrot, John and Eleftheriou, Nikolas and Roswall, Pernilla and Cordero, Eugenia and Lindström, Linda and Bartoschek, Michael and Haller, B Kristian and Pearsall, R Scott and Mulivor, Aaron W and Kumar, Ravindra and Larsson, Christer and Bergh, Jonas and Pietras, Kristian},
  issn         = {1538-7445},
  language     = {eng},
  number       = {12},
  pages        = {2445--2456},
  publisher    = {American Association for Cancer Research Inc.},
  series       = {Cancer Research},
  title        = {Endothelial ALK1 Is a Therapeutic Target to Block Metastatic Dissemination of Breast Cancer.},
  url          = {http://dx.doi.org/10.1158/0008-5472.CAN-14-3706},
  volume       = {75},
  year         = {2015},
}