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Mol Oncol. 2014 Sep 12;8(6):1095-111. doi: 10.1016/j.molonc.2014.06.005. Epub 2014 Jul 10.

Tumour heterogeneity and the evolution of polyclonal drug resistance.

Author information

1
Translational Cancer Therapeutics Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3L7, UK; UCL Cancer Institute, Paul O'Gorman Building University College London, 72 Huntley Street, London WC1E 6DD, UK. Electronic address: r.burrell@ucl.ac.uk.
2
Translational Cancer Therapeutics Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3L7, UK; UCL Cancer Institute, Paul O'Gorman Building University College London, 72 Huntley Street, London WC1E 6DD, UK. Electronic address: charles.swanton@cancer.org.uk.

Abstract

Cancer drug resistance is a major problem, with the majority of patients with metastatic disease ultimately developing multidrug resistance and succumbing to their disease. Our understanding of molecular events underpinning treatment failure has been enhanced by new genomic technologies and pre-clinical studies. Intratumour genetic heterogeneity (ITH) is a prominent contributor to therapeutic failure, and it is becoming increasingly apparent that individual tumours may achieve resistance via multiple routes simultaneously - termed polyclonal resistance. Efforts to target single resistance mechanisms to overcome therapeutic failure may therefore yield only limited success. Clinical studies with sequential analysis of tumour material are needed to enhance our understanding of inter-clonal functional relationships and tumour evolution during therapy, and to improve drug development strategies in cancer medicine.

KEYWORDS:

Cancer evolution; Drug resistance; Genomic instability; Intratumour heterogeneity

PMID:
25087573
PMCID:
PMC5528620
DOI:
10.1016/j.molonc.2014.06.005
[Indexed for MEDLINE]
Free PMC Article

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