期刊
MOLECULAR ONCOLOGY
卷 8, 期 6, 页码 1095-1111出版社
WILEY
DOI: 10.1016/j.molonc.2014.06.005
关键词
Intratumour heterogeneity; Drug resistance; Genomic instability; Cancer evolution
类别
资金
- Cancer Research UK [A19310, A17786]
- Rosetrees Trust
- EU FP7 (project PREDICT) [259303]
- EU FP7 (project RESPONSIFY) [259303]
- Prostate Cancer Foundation
- European Research Council
- Breast Cancer Research Foundation
- National Institute for Health Research University College London Hospitals Biomedical Research Centre
- Cancer Research UK [17786, 19310] Funding Source: researchfish
- Medical Research Council [G0701935] Funding Source: researchfish
- MRC [G0701935] Funding Source: UKRI
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. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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