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Cancer Cell. 2015 Jan 12;27(1):123-37. doi: 10.1016/j.ccell.2014.10.015.

Dual-action combination therapy enhances angiogenesis while reducing tumor growth and spread.

Author information

1
Centre for Tumor Biology, Barts Cancer Institute-a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
2
Centre for Haemato-Oncology, Barts Cancer Institute-a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
3
Centre for Molecular Oncology, Barts Cancer Institute-a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
4
CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
5
Mary Lyon Centre, MRC Harwell, Harwell Science and Innovation Campus, Oxfordshire OX11 0RD, UK.
6
Centre for Cancer Inflammation, Barts Cancer Institute-a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK; Barts and the London HPB Centre, The Royal London Hospital, Barts Health NHS Trust, London E1 1BB, UK.
7
Centre for Tumor Biology, Barts Cancer Institute-a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK; Barts and the London HPB Centre, The Royal London Hospital, Barts Health NHS Trust, London E1 1BB, UK.
8
Centre for Tumor Biology, Barts Cancer Institute-a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK. Electronic address: k.hodivala-dilke@qmul.ac.uk.

Abstract

Increasing chemotherapy delivery to tumors, while enhancing drug uptake and reducing side effects, is a primary goal of cancer research. In mouse and human cancer models in vivo, we show that coadministration of low-dose Cilengitide and Verapamil increases tumor angiogenesis, leakiness, blood flow, and Gemcitabine delivery. This approach reduces tumor growth, metastasis, and minimizes side effects while extending survival. At a molecular level, this strategy alters Gemcitabine transporter and metabolizing enzyme expression levels, enhancing the potency of Gemcitabine within tumor cells in vivo and in vitro. Thus, the dual action of low-dose Cilengitide, in vessels and tumor cells, improves chemotherapy efficacy. Overall, our data demonstrate that vascular promotion therapy is a means to improve cancer treatment.

PMID:
25584895
DOI:
10.1016/j.ccell.2014.10.015
[Indexed for MEDLINE]
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