| Title: |
Combine and conquer: challenges for targeted therapy combinations in early phase trials. |
| Authors: |
Lopez, JS; Banerji, U |
| Contributors: |
Lopez, Juanita; Banerji, Udai |
| Publisher Information: |
NATURE PORTFOLIO |
| Publication Year: |
2016 |
| Collection: |
The Institute of Cancer Research (ICR): Publications Repository |
| Subject Terms: |
Cell Line; Tumor; Immune System; Humans; Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Systems Biology; Drug Resistance; Neoplasm; Patient Selection; Clinical Trials as Topic; Molecular Targeted Therapy; Tumor Microenvironment |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
Print-Electronic; 66; application/pdf |
| Language: |
English |
| ISSN: |
1759-4782; 1759-4774 |
| Relation: |
Nature reviews. Clinical oncology, 2017, 14 (1), pp. 57 - 66; https://repository.icr.ac.uk/handle/internal/68 |
| DOI: |
10.1038/nrclinonc.2016.96 |
| Availability: |
https://doi.org/10.1038/nrclinonc.2016.96; https://repository.icr.ac.uk/handle/internal/68 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 |
| Accession Number: |
edsbas.26E78585 |
| Database: |
BASE |