Journal article
Modelling longitudinal preclinical tumour size data to identify transient dynamics in tumour response to anti-angiogenic drugs
- Abstract:
- Experimental evidence suggests that antiangiogenic therapy gives rise to a transient window of vessel normalization, within which the efficacy of radiotherapy and chemotherapy may be enhanced. Preclinical experiments that measure components of vessel normalization are invasive and expensive. We have developed a mathematical model of vascular tumor growth from preclinical time‐course data in a breast cancer xenograft model. We used a mixed‐effects approach for model parameterization, leveraging tumor size data to identify a period of enhanced tumor growth that could potentially correspond to the transient window of vessel normalization. We estimated the characteristics of the window for mice treated with an anti‐VEGF antibody (bevacizumab) or with a bispecific anti‐VEGF/anti‐angiopoietin‐2 antibody (vanucizumab). We show how the mathematical model could theoretically be used to predict how to coordinate antiangiogenic therapy with radiotherapy or chemotherapy to maximize therapeutic effect, reducing the need for preclinical experiments that directly measure vessel normalization parameters.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Publisher copy:
- 10.1002/psp4.12142
Authors
+ F. Hoffman La-Roche Ltd
More from this funder
- Funding agency for:
- Hutchinson, L
- Grant:
- EP/G037280/1
+ Engineering
and Physical Sciences Research Council
More from this funder
- Funding agency for:
- Hutchinson, L
- Grant:
- EP/G037280/1
+ Systems Approaches
to Biomedical Sciences Centre for Doctoral Training (SABS-CDT)
More from this funder
- Funding agency for:
- Hutchinson, L
- Grant:
- EP/G037280/1
- Publisher:
- Wiley
- Journal:
- CPT: Pharmacometrics and Systems Pharmacology More from this journal
- Volume:
- 5
- Issue:
- 11
- Pages:
- 636-645
- Publication date:
- 2016-11-14
- Acceptance date:
- 2016-09-28
- DOI:
- ISSN:
-
2163-8306
- Keywords:
- Pubs id:
-
pubs:646458
- UUID:
-
uuid:9aebeac0-f118-45a1-94f6-3fc626e316dd
- Local pid:
-
pubs:646458
- Source identifiers:
-
646458
- Deposit date:
-
2016-09-28
Terms of use
- Copyright holder:
- Hutchinson et al
- Copyright date:
- 2016
- Notes:
-
Copyright © 2016 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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