Combining hypoxia-activated prodrugs and radiotherapy in silico: Impact of treatment scheduling and the intra-tumoural oxygen landscape.
Journal
PLoS computational biology
ISSN: 1553-7358
Titre abrégé: PLoS Comput Biol
Pays: United States
ID NLM: 101238922
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
29
11
2019
accepted:
11
06
2020
revised:
13
08
2020
pubmed:
4
8
2020
medline:
12
9
2020
entrez:
4
8
2020
Statut:
epublish
Résumé
Hypoxia-activated prodrugs (HAPs) present a conceptually elegant approach to not only overcome, but better yet, exploit intra-tumoural hypoxia. Despite being successful in vitro and in vivo, HAPs are yet to achieve successful results in clinical settings. It has been hypothesised that this lack of clinical success can, in part, be explained by the insufficiently stringent clinical screening selection of determining which tumours are suitable for HAP treatments. Taking a mathematical modelling approach, we investigate how tumour properties and HAP-radiation scheduling influence treatment outcomes in simulated tumours. The following key results are demonstrated in silico: (i) HAP and ionising radiation (IR) monotherapies may attack tumours in dissimilar, and complementary, ways. (ii) HAP-IR scheduling may impact treatment efficacy. (iii) HAPs may function as IR treatment intensifiers. (iv) The spatio-temporal intra-tumoural oxygen landscape may impact HAP efficacy. Our in silico framework is based on an on-lattice, hybrid, multiscale cellular automaton spanning three spatial dimensions. The mathematical model for tumour spheroid growth is parameterised by multicellular tumour spheroid (MCTS) data.
Identifiants
pubmed: 32745136
doi: 10.1371/journal.pcbi.1008041
pii: PCOMPBIOL-D-19-02094
pmc: PMC7425994
doi:
Substances chimiques
Antineoplastic Agents
0
Prodrugs
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008041Subventions
Organisme : Medical Research Council
ID : MR/R017506/1
Pays : United Kingdom
Organisme : CIHR
Pays : Canada
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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