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Inhibition of the Src Oncogene: Therapeutic Potential in Ovarian Carcinoma

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Book cover Emerging Therapeutic Targets in Ovarian Cancer

Abstract

Src, a non-receptor tyrosine kinase, is the convergence point for multiple cellular pathways vital for tumorigenesis. It is a key regulator of angiogenesis with indirect effects exerted through VEGF. Additional potent pro-angiogenic cytokines such as IL-6 and IL-8 act via Src as well. Src also directly affects vascular permeability by impacting endothelial cadherin function, thereby inducing vascular leakage of tumor and interstitial fluid. Furthermore, with downstream targets such as FAK, Src orchestrates cell migration and integrin functions, which collectively contribute to the metastatic phenotype. Overexpression of Src is associated with advanced ovarian cancers, and the role of chemoresistance is of special interest as Src inhibition appears to reverse platinum-resistance, in part, by upregulation of caspase-3-mediated apoptosis. Src is an attractive target in ovarian cancers, and current trials using various Src inhibitors are underway.

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Acknowledgments

This work is partially funded by The Fulbright Commission-Fulbright Distinguished Scholar awarded to LYH, Council for International Exchange of Scholars, Department of State, Washington D.C., and supported in part by NIH (CA110793, CA109298, P50 CA083639, P50 CA098258, CA128797, RC2GM092599, U54 CA151668), DOD (OC73399, W81XWH-10-1-0158, BC 085265), the EIF Foundation, the Ovarian Cancer Research Fund Program Project Development Grant, the Zarrow Foundation, the Marcus Foundation, and the Betty Ann Asche Murray Distinguished Professorship.

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Authors and Affiliations

  1. Drug Development Unit, The Royal Marsden Hospital, London, UK

    Liz Y. Han

  2. Departments of Gynecologic Oncology and Cancer Biology, Center for RNA Interference and Non-coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX, 77230-1439, USA

    Anil K. Sood

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  1. Liz Y. Han
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Correspondence to Anil K. Sood .

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Editors and Affiliations

  1. Royal Marsden Hospital, Drug Development Unit, Institute of Cancer Research, Sutton, SM2 5PT, United Kingdom

    Stan Kaye

  2. , Department of Surgery and Cancer, Imperial College London, London, W12 0NN, United Kingdom

    Robert Brown

  3. , Department of Surgery and Cancer, Imperial College, London, W12 0NN, United Kingdom

    Hani Gabra

  4. , Department of Medicine, Royal Marsden Hospital, London, SW3 6JJ, United Kingdom

    Martin Gore

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Han, L.Y., Sood, A.K. (2011). Inhibition of the Src Oncogene: Therapeutic Potential in Ovarian Carcinoma. In: Kaye, S., Brown, R., Gabra, H., Gore, M. (eds) Emerging Therapeutic Targets in Ovarian Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7216-3_5

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