Universität zu Köln

Chatterjee, Sampurna, Wieczorek, Caroline, Schoettle, Jakob, Siobal, Maike, Hinze, Yvonne, Franz, Thomas, Florin, Alexandra, Adamczak, Joanna, Heukamp, Lukas C., Neumaier, Bernd ORCID: 0000-0001-5425-3116 and Ullrich, Roland T. (2014). Transient Antiangiogenic Treatment Improves Delivery of Cytotoxic Compounds and Therapeutic Outcome in Lung Cancer. Cancer Res., 74 (10). S. 2816 - 2825. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 1538-7445

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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 [O-15] 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. Cancer Res; 74(10); 2816-24. (C) 2014 AACR.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Chatterjee, Sampurna UNSPECIFIED UNSPECIFIED UNSPECIFIED Wieczorek, Caroline UNSPECIFIED UNSPECIFIED UNSPECIFIED Schoettle, Jakob UNSPECIFIED UNSPECIFIED UNSPECIFIED Siobal, Maike UNSPECIFIED UNSPECIFIED UNSPECIFIED Hinze, Yvonne UNSPECIFIED UNSPECIFIED UNSPECIFIED Franz, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Florin, Alexandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Adamczak, Joanna UNSPECIFIED UNSPECIFIED UNSPECIFIED Heukamp, Lukas C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Neumaier, Bernd UNSPECIFIED orcid.org/0000-0001-5425-3116 UNSPECIFIED Ullrich, Roland T. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-438291
DOI:	10.1158/0008-5472.CAN-13-2986
Journal or Publication Title:	Cancer Res.
Volume:	74
Number:	10
Page Range:	S. 2816 - 2825
Date:	2014
Publisher:	AMER ASSOC CANCER RESEARCH
Place of Publication:	PHILADELPHIA
ISSN:	1538-7445
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language POSITRON-EMISSION-TOMOGRAPHY; VASCULAR NORMALIZATION; TUMOR MICROENVIRONMENT; ANGIOGENESIS; OXYGENATION; METASTASIS; INHIBITION; APRICOXIB; PERICYTES; VESSELS Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43829