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Transient Antiangiogenic Treatment Improves Delivery of Cytotoxic Compounds and Therapeutic Outcome in Lung Cancer

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:
    CreatorsEmail
    Chatterjee, Sampurnasampurna.steele@gmail.com
    URN: urn:nbn:de:hbz:38-65927
    Journal or Publication Title: Cancer Research
    Subjects: Natural sciences and mathematics
    Life sciences
    Faculty: Mathematisch-Naturwissenschaftliche Fakultät
    Divisions: Mathematisch-Naturwissenschaftliche Fakultät > ZMMK
    Language: English
    Date: 2014
    Date Type: Completion
    Full Text Status: Public
    Related URLs:
    Date Deposited: 05 Apr 2016 13:54:18
    URI: http://kups.ub.uni-koeln.de/id/eprint/6592

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