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Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2909-14. doi: 10.1073/pnas.1018892108. Epub 2011 Jan 31.

Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors.

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  • 1Department of Radiation Oncology, Edwin L. Steele Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

Abstract

The dense collagen network in tumors significantly reduces the penetration and efficacy of nanotherapeutics. We tested whether losartan--a clinically approved angiotensin II receptor antagonist with noted antifibrotic activity--can enhance the penetration and efficacy of nanomedicine. We found that losartan inhibited collagen I production by carcinoma-associated fibroblasts isolated from breast cancer biopsies. Additionally, it led to a dose-dependent reduction in stromal collagen in desmoplastic models of human breast, pancreatic, and skin tumors in mice. Furthermore, losartan improved the distribution and therapeutic efficacy of intratumorally injected oncolytic herpes simplex viruses. Finally, it also enhanced the efficacy of i.v. injected pegylated liposomal doxorubicin (Doxil). Thus, losartan has the potential to enhance the efficacy of nanotherapeutics in patients with desmoplastic tumors.

PMID:
21282607
[PubMed - indexed for MEDLINE]
PMCID:
PMC3041115
Free PMC Article
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