Universität zu Köln

Chatterjee, Sampurna (2014). Transient Antiangiogenic Treatment Improves Delivery of Cytotoxic Compounds and Therapeutic Outcome in Lung Cancer. Cancer Research.

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Abstract

Extensive oncologic experience argues that the most efficacious applications of antiangiogenic agents rely upon a combination with cytotoxic drugs. Yet there remains a lack of clarity about how to optimize scheduling for such drug combinations. Prudent antiangiogenic therapy might transiently normalize blood vessels to improve tumor oxygenation and drug exposure. Using [15O]H2O positron emission tomography imaging in a preclinical mouse model of non–small cell lung cancer, we observed that short-term treatment with the vascular endothelial growth factor receptor/platelet-derived growth factor receptor inhibitor PTK787 licensed a transient window of improved tumor blood flow. The improvement observed was associated with a reduced leakiness from tumor vessels, consistent with induction of a vascular normalization process. Initiation of a cytotoxic treatment in this window of tumor vessel normalization resulted in increased efficacy, as illustrated by improved outcomes of erlotinib administration after initial PTK787 treatment. Notably, intermittent PTK787 treatment also facilitated long-term tumor regression. In summary, our findings offer strong evidence that short-term antiangiogenic therapy can promote a transient vessel normalization process that improves the delivery and efficacy of a targeted cytotoxic drug.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Chatterjee, Sampurna sampurna.steele@gmail.com UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-65927
Journal or Publication Title:	Cancer Research
Date:	2014
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Zentrum für Molekulare Medizin
Subjects:	Natural sciences and mathematics Life sciences
Related URLs:	http://cancerres.aacrjournals.org/conten...
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/6592