Combine and conquer: challenges for targeted therapy combinations in early phase trials.
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Embargo End Date
ICR Authors
Authors
Lopez, JS
Banerji, U
Banerji, U
Document Type
Journal Article
Date
2017-01-01
Date Accepted
2016-05-26
Abstract
Our increasing understanding of cancer biology has led to the development of molecularly targeted anticancer drugs. The full potential of these agents has not, however, been realised, owing to the presence of de novo (intrinsic) resistance, often resulting from compensatory signalling pathways, or the development of acquired resistance in cancer cells via clonal evolution under the selective pressures of treatment. Combinations of targeted treatments can circumvent some mechanisms of resistance to yield a clinical benefit. We explore the challenges in identifying the best drug combinations and the best combination strategies, as well as the complexities of delivering these treatments to patients. Recognizing treatment-induced toxicity and the inability to use continuous pharmacodynamically effective doses of many targeted treatments necessitates creative intermittent scheduling. Serial tumour profiling and the use of parallel co-clinical trials can contribute to understanding mechanisms of resistance, and will guide the development of adaptive clinical trial designs that can accommodate hypothesis testing, in order to realize the full potential of combination therapies.
Citation
Nature reviews. Clinical oncology, 2017, 14 (1), pp. 57 - 66
Source Title
Publisher
NATURE PORTFOLIO
ISSN
1759-4774
eISSN
1759-4782
Collections
Research Team
Medicine (de Bono Prostate)
Clinical Pharmacology – Adaptive Therapy
Medicine Drug Development Unit (de Bono)
Clinical Pharmacology – Adaptive Therapy
Medicine Drug Development Unit (de Bono)