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Maria Eugenia Cordero Concha

Biomedical analyst

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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

Summary, in 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.

Department/s

  • Division of Translational Cancer Research
  • Experimental oncology
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

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.

Topic

  • Cancer and Oncology

Status

Published

Research group

  • Experimental oncology

ISBN/ISSN/Other

  • ISSN: 1538-7445