Role of intratumoural heterogeneity in cancer drug resistance: Molecular and clinical perspectives

Saunders, Nicholas A., Simpson, Fiona, Thompson, Erik W., Hill, Michelle M., Endo-Munoz, Liliana, Leggatt, Graham, Minchin, Rodney F. and Guminski, Alexander (2012) Role of intratumoural heterogeneity in cancer drug resistance: Molecular and clinical perspectives. EMBO Molecular Medicine, 4 8: 675-684. doi:10.1002/emmm.201101131

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Author Saunders, Nicholas A.
Simpson, Fiona
Thompson, Erik W.
Hill, Michelle M.
Endo-Munoz, Liliana
Leggatt, Graham
Minchin, Rodney F.
Guminski, Alexander
Title Role of intratumoural heterogeneity in cancer drug resistance: Molecular and clinical perspectives
Journal name EMBO Molecular Medicine   Check publisher's open access policy
ISSN 1757-4684
Publication date 2012
Sub-type Article (original research)
DOI 10.1002/emmm.201101131
Open Access Status DOI
Volume 4
Issue 8
Start page 675
End page 684
Total pages 10
Place of publication Weinheim, Germany
Publisher Wiley
Collection year 2013
Language eng
Abstract Drug resistance continues to be a major barrier to the delivery of curative therapies in cancer. Historically, drug resistance has been associated with over-expression of drug transporters, changes in drug kinetics or amplification of drug targets. However, the emergence of resistance in patients treated with new-targeted therapies has provided new insight into the complexities underlying cancer drug resistance. Recent data now implicate intratumoural heterogeneity as a major driver of drug resistance. Single cell sequencing studies that identified multiple genetically distinct variants within human tumours clearly demonstrate the heterogeneous nature of human tumours. The major contributors to intratumoural heterogeneity are (i) genetic variation, (ii) stochastic processes, (iii) the microenvironment and (iv) cell and tissue plasticity. Each of these factors impacts on drug sensitivity. To deliver curative therapies to patients, modification of current therapeutic strategies to include methods that estimate intratumoural heterogeneity and plasticity will be essential.
Keyword Chemotherapy
Clonal variants
Drug resistance
Intratumoural heterogeneity
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article first published online: 25 JUN 2012

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
ERA White List Items
School of Biomedical Sciences Publications
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 50 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 29 Jun 2012, 15:56:24 EST by Bacsweet Kaur on behalf of School of Biomedical Sciences