Modelling longitudinal preclinical tumour size data to identify transient dynamics in tumour response to anti-angiogenic drugs

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...

Descrición completa

Detalles Bibliográficos
Main Authors: Hutchinson, L, Mueller, H, Gaffney, E, Maini, P, Wagg, J, Phipps, A, Boetsch, C, Byrne, H, Ribba, B
Formato: Journal article
Publicado: Wiley 2016
_version_ 1826287093812297728
author Hutchinson, L
Mueller, H
Gaffney, E
Maini, P
Wagg, J
Phipps, A
Boetsch, C
Byrne, H
Ribba, B
author_facet Hutchinson, L
Mueller, H
Gaffney, E
Maini, P
Wagg, J
Phipps, A
Boetsch, C
Byrne, H
Ribba, B
author_sort Hutchinson, L
collection OXFORD
description 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.
first_indexed 2024-03-07T01:53:28Z
format Journal article
id oxford-uuid:9aebeac0-f118-45a1-94f6-3fc626e316dd
institution University of Oxford
last_indexed 2024-03-07T01:53:28Z
publishDate 2016
publisher Wiley
record_format dspace
spelling oxford-uuid:9aebeac0-f118-45a1-94f6-3fc626e316dd2022-03-27T00:24:48ZModelling longitudinal preclinical tumour size data to identify transient dynamics in tumour response to anti-angiogenic drugsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9aebeac0-f118-45a1-94f6-3fc626e316ddSymplectic Elements at OxfordWiley2016Hutchinson, LMueller, HGaffney, EMaini, PWagg, JPhipps, ABoetsch, CByrne, HRibba, BExperimental 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.
spellingShingle Hutchinson, L
Mueller, H
Gaffney, E
Maini, P
Wagg, J
Phipps, A
Boetsch, C
Byrne, H
Ribba, B
Modelling longitudinal preclinical tumour size data to identify transient dynamics in tumour response to anti-angiogenic drugs
title Modelling longitudinal preclinical tumour size data to identify transient dynamics in tumour response to anti-angiogenic drugs
title_full Modelling longitudinal preclinical tumour size data to identify transient dynamics in tumour response to anti-angiogenic drugs
title_fullStr Modelling longitudinal preclinical tumour size data to identify transient dynamics in tumour response to anti-angiogenic drugs
title_full_unstemmed Modelling longitudinal preclinical tumour size data to identify transient dynamics in tumour response to anti-angiogenic drugs
title_short Modelling longitudinal preclinical tumour size data to identify transient dynamics in tumour response to anti-angiogenic drugs
title_sort modelling longitudinal preclinical tumour size data to identify transient dynamics in tumour response to anti angiogenic drugs
work_keys_str_mv AT hutchinsonl modellinglongitudinalpreclinicaltumoursizedatatoidentifytransientdynamicsintumourresponsetoantiangiogenicdrugs
AT muellerh modellinglongitudinalpreclinicaltumoursizedatatoidentifytransientdynamicsintumourresponsetoantiangiogenicdrugs
AT gaffneye modellinglongitudinalpreclinicaltumoursizedatatoidentifytransientdynamicsintumourresponsetoantiangiogenicdrugs
AT mainip modellinglongitudinalpreclinicaltumoursizedatatoidentifytransientdynamicsintumourresponsetoantiangiogenicdrugs
AT waggj modellinglongitudinalpreclinicaltumoursizedatatoidentifytransientdynamicsintumourresponsetoantiangiogenicdrugs
AT phippsa modellinglongitudinalpreclinicaltumoursizedatatoidentifytransientdynamicsintumourresponsetoantiangiogenicdrugs
AT boetschc modellinglongitudinalpreclinicaltumoursizedatatoidentifytransientdynamicsintumourresponsetoantiangiogenicdrugs
AT byrneh modellinglongitudinalpreclinicaltumoursizedatatoidentifytransientdynamicsintumourresponsetoantiangiogenicdrugs
AT ribbab modellinglongitudinalpreclinicaltumoursizedatatoidentifytransientdynamicsintumourresponsetoantiangiogenicdrugs