Endothelial ALK1 Is a Therapeutic Target to Block Metastatic Dissemination of Breast Cancer.
Författare
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.
Avdelning/ar
- Avdelningen för translationell cancerforskning
- Experimentell onkologi
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publiceringsår
2015
Språk
Engelska
Sidor
2445-2456
Publikation/Tidskrift/Serie
Cancer Research
Volym
75
Issue
12
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
American Association for Cancer Research Inc.
Ämne
- Cancer and Oncology
Status
Published
Forskningsgrupp
- Experimental oncology
ISBN/ISSN/Övrigt
- ISSN: 1538-7445