uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Activin Receptor-like Kinase 1 Ligand Trap Reduces Microvascular Density and Improves Chemotherapy Efficiency to Various Solid Tumors
Leiden Univ, Med Ctr, Dept Mol Cell Biol, NL-2300 RC Leiden, Netherlands.;Leiden Univ, Med Ctr, Canc Genom Ctr Netherlands, NL-2300 RC Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gastroenterol Hepatol, NL-2300 RC Leiden, Netherlands..
Leiden Univ, Med Ctr, Dept Mol Cell Biol, NL-2300 RC Leiden, Netherlands.;Leiden Univ, Med Ctr, Canc Genom Ctr Netherlands, NL-2300 RC Leiden, Netherlands..
Leiden Univ, Med Ctr, Dept Mol Cell Biol, NL-2300 RC Leiden, Netherlands.;Leiden Univ, Med Ctr, Canc Genom Ctr Netherlands, NL-2300 RC Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gastroenterol Hepatol, NL-2300 RC Leiden, Netherlands..
Leiden Univ, Med Ctr, Dept Mol Cell Biol, NL-2300 RC Leiden, Netherlands.;Leiden Univ, Med Ctr, Canc Genom Ctr Netherlands, NL-2300 RC Leiden, Netherlands..
Show others and affiliations
2016 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 22, no 1, 96-106 p.Article in journal (Refereed) Published
Resource type
Text
Abstract [en]

Purpose: Antiangiogenic therapy, mostly targeting VEGF, has been applied in cancer patients for the last decade. However, resistance to anti-VEGF therapy and/or no significant benefit as monotherapeutic agent is often observed. Therefore, new antiangiogenic strategies are needed. In the current study, we investigated the therapeutic effect of interfering with the bone morphogenetic protein (BMP)9/activin receptor-like kinase (ALK)1 signaling pathway by using an ALK1-Fc ligand trap. Experimental Design: We analyzed the potential antiangiogenic and antitumor effects of ALK1-Fc protein as monotherapy and in combination with chemotherapy in vivo in mouse models of melanoma, head and neck cancer, and invasive lobular breast carcinomas. ALK1-Fc sequesters BMP9 and 10 and prevents binding of these ligands to endothelial ALK1, which regulates angiogenesis. Results: Treatment of mice with ALK1-Fc strongly decreased the tumors' microvascular density in the three different mouse cancer models. However, this effect was not accompanied by a reduction in tumor volume. Animmunohistochemical analysis of the tumor samples revealed that ALK1-Fc treatment increased the pericyte coverage of the remaining tumor vessels and decreased the hypoxia within the tumor. Next, we observed that combining ALK1-Fc with cisplatin inhibited tumor growth in the breast and head and neck cancer models more efficiently than chemotherapy alone. Conclusions: The addition of ALK1-Fc to the cisplatin treatment was able to enhance the cytotoxic effect of the chemotherapy. Our results provide strong rationale to explore combined targeting of ALK1 with chemotherapy in a clinical setting, especially in the ongoing phase II clinical trials with ALK1-Fc.

Place, publisher, year, edition, pages
2016. Vol. 22, no 1, 96-106 p.
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-274904DOI: 10.1158/1078-0432.CCR-15-0743ISI: 000367550300014PubMedID: 26373572OAI: oai:DiVA.org:uu-274904DiVA: diva2:898263
Funder
Swedish Cancer SocietyEU, European Research Council
Available from: 2016-01-27 Created: 2016-01-26 Last updated: 2017-11-30Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Department of Medical Sciences
In the same journal
Clinical Cancer Research
Cancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 209 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf