Angiostatic treatment prior to chemo- or photodynamic therapy improves anti-tumor efficacy

Scientific Reports
Andrea WeissPatrycja Nowak-Sliwinska

Abstract

Tumor vasculature is known to be poorly organized leading to increased leakage of molecules to the extravascular space. This process can potentially increase interstitial fluid pressure impairing intra-tumoral blood flow and oxygen supply, and can affect drug uptake. Anti-angiogenic therapies are believed to reduce vascular permeability, potentially reducing interstitial fluid pressure and improving the extravasation of small molecule-based chemotherapeutics. Here we show that pretreatment of human ovarian carcinoma tumors with sub-optimal doses of the VEGFR targeting tyrosine kinase inhibitor axitinib, but not the EGFR targeting kinase inhibitor erlotinib, induces a transient period of increased tumor oxygenation. Doxorubicin administered within this window was found to enter the extravascular tumor space more rapidly compared to doxorubicin when applied alone or outside this time window. Treatment with the chemotherapeutics, doxorubicin and RAPTA-C, as well as applying photodynamic therapy during this period of elevated oxygenation led to enhanced tumor growth inhibition. Improvement of therapy was not observed when applied outside the window of increased oxygenation. Taken together, these findings further confirm the hypothe...Continue Reading

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Citations

Feb 13, 2016·Journal of Translational Medicine·Joji IidaCraig D Shriver
Dec 28, 2016·SLAS Technology·Andrea Weiss, Patrycja Nowak-Sliwinska
Jan 18, 2017·Journal of Laboratory Automation·Andrea Weiss, Patrycja Nowak-Sliwinska
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Jul 18, 2020·International Journal of Molecular Sciences·Caroline GoupilleKarine Mahéo
Jul 21, 2015·ChemMedChem·Emilia PăunescuPaul J Dyson
Dec 20, 2017·Dalton Transactions : an International Journal of Inorganic Chemistry·Fabio MarchettiPaul J Dyson
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Aug 6, 2017·Journal of Inorganic Biochemistry·Emilia PăunescuPaul J Dyson
Oct 21, 2017·Inorganic Chemistry·Agnese PetriniPaul J Dyson
Sep 29, 2021·Advanced Materials·Yilin WanPeng Huang

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