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

Author:
  • Sara I Cunha
  • Matteo Bocci
  • John Lövrot
  • Nikolas Eleftheriou
  • Pernilla Roswall
  • Eugenia Cordero
  • Linda Lindström
  • Michael Bartoschek
  • B Kristian Haller
  • R Scott Pearsall
  • Aaron W Mulivor
  • Ravindra Kumar
  • Christer Larsson
  • Jonas Bergh
  • Kristian Pietras
Publishing year: 2015
Language: English
Pages: 2445-2456
Publication/Series: Cancer Research
Volume: 75
Issue: 12
Document type: Journal article
Publisher: American Association for Cancer Research Inc.

Abstract english

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.

Keywords

  • Cancer and Oncology

Other

Published
  • Experimental oncology
  • ISSN: 1538-7445
Kristian Pietras
E-mail: kristian [dot] pietras [at] med [dot] lu [dot] se

Professor

Division of Translational Cancer Research

+46 46 222 64 29

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Project manager

Experimental oncology