Concise Review: Cancer Cells Escape from Oncogene Addiction: Understanding the Mechanisms Behind Treatment Failure for More Effective Targeting

Authors

  • Francesca Pellicano,

    1. Paul O'Gorman Leukaemia Research Centre, Institute of Cancer Sciences, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, United Kingdom
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  • Leena Mukherjee,

    1. Paul O'Gorman Leukaemia Research Centre, Institute of Cancer Sciences, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, United Kingdom
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  • Tessa L. Holyoake

    Corresponding author
    1. Paul O'Gorman Leukaemia Research Centre, Institute of Cancer Sciences, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, United Kingdom
    • Correspondence: Tessa L. Holyoake, MBChB, MRCP, MRCPath, PhD, FRCP, FRCPath, RSE, Gartnavel General Hospital, 21 Shelley Road, Glasgow, G12 0ZD, U.K. Telephone: +141–301-7880; Fax: +141–301-7898; e-mail: Tessa.Holyoake@glasgow.ac.uk

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Abstract

Oncogene addiction describes the dependence of some cancers on one or a few genes for their survival. Inhibition of the corresponding oncoproteins can lead to dramatic responses. However, in some cases, such as chronic myeloid leukemia (CML), a disease characterized by the presence of the abnormal fusion tyrosine kinase BCR-ABL, cancer stem cells may never acquire addiction to the oncogene that drives disease development. The suggested mechanism(s) for treatment failure include a quiescent stem cell population capable of reinstating disease, high levels of oncoprotein expression, or acquired mutations in the oncogene. In this review, we discuss the evidence for oncogene addiction in several solid tumors and their potential escape mechanism(s) with a particular focus on CML stem cells. Stem Cells 2014;32:1373–1379

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