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Receptor Tyrosine Kinases and Drug Resistance: Development and Characterization of In Vitro Models of Resistance to RTK Inhibitors

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Receptor Tyrosine Kinases

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1233))

Abstract

Aberrant expression of receptor tyrosine kinases (RTKs) has been extensively associated with alterations in the physiological activities of cells. These include cell growth and differentiation, cell death/survival, and the motility of cells which can subsequently lead to emergence of various diseases including cancer. Recent advances in the treatment of cancer have involved using RTKs as therapeutic targets. Unfortunately, the clinical use of receptor tyrosine kinase inhibitors (RTKIs) for the treatment of cancer has been hindered by innate or acquired resistance among some patients, as also experienced with classical chemotherapy. It has become apparent that the deregulated expression of RTKs may play a significant part in driving this resistance. In order to fully elucidate the role of RTKs in drug resistance, the use of preclinical models has helped to mimic this clinical problem. In this chapter, we describe the methods associated with establishing and characterizing cell line models of drug resistance to the dual RTKI, lapatinib. These methods include the assessment of lapatinib resistance; cross-resistance to other RTKIs; the alteration of RTK expression; and other associated phenotypic changes such as cellular migration, invasion, and anoikis sensitivity/resistance.

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Acknowledgements

Science Foundation Ireland funding to Molecular Therapeutics for Cancer, Ireland (08/SRC/B1410); Higher Education Authority PRTLI Cycle 5 funding to Trinity Biomedical Sciences Institute; and Irish Cancer Society’s funding to Breast-Predict [CCRC13GAL].

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Authors and Affiliations

  1. School of Pharmacy & Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland

    Claire Corcoran & Lorraine O’Driscoll

Authors
  1. Claire Corcoran
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  2. Lorraine O’Driscoll
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Corresponding author

Correspondence to Lorraine O’Driscoll .

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Editors and Affiliations

  1. Necker Hospital, Paris, France

    Serena Germano

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© 2015 Springer Science+Business Media New York

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Corcoran, C., O’Driscoll, L. (2015). Receptor Tyrosine Kinases and Drug Resistance: Development and Characterization of In Vitro Models of Resistance to RTK Inhibitors. In: Germano, S. (eds) Receptor Tyrosine Kinases. Methods in Molecular Biology, vol 1233. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1789-1_16

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  • DOI: https://doi.org/10.1007/978-1-4939-1789-1_16

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-1788-4

  • Online ISBN: 978-1-4939-1789-1

  • eBook Packages: Springer Protocols

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