Endothelial ALK1 Is a Therapeutic Target to Block Metastatic Dissemination of Breast Cancer.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/7485927
- author
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cancer Research
- volume
- 75
- issue
- 12
- pages
- 2445 - 2456
- publisher
- American Association for Cancer Research Inc.
- external identifiers
-
- pmid:26077471
- wos:000357334400006
- scopus:84941736038
- pmid:26077471
- ISSN
- 1538-7445
- DOI
- 10.1158/0008-5472.CAN-14-3706
- language
- English
- LU publication?
- yes
- id
- deefdc5f-3e9c-4f9b-ab10-9647ee566a54 (old id 7485927)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/26077471?dopt=Abstract
- date added to LUP
- 2016-04-01 10:40:41
- date last changed
- 2024-02-21 22:12:22
@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}}, doi = {{10.1158/0008-5472.CAN-14-3706}}, volume = {{75}}, year = {{2015}}, }