Title
Quantifying the effects of antiangiogenic and chemotherapy drug combinations on drug delivery and treatment efficacy.
Abstract
Tumor-induced angiogenesis leads to the development of leaky tumor vessels devoid of structural and morphological integrity. Due to angiogenesis, elevated interstitial fluid pressure (IFP) and low blood perfusion emerge as common properties of the tumor microenvironment that act as barriers for drug delivery. In order to overcome these barriers, normalization of vasculature is considered to be a viable option. However, insight is needed into the phenomenon of normalization and in which conditions it can realize its promise. In order to explore the effect of microenvironmental conditions and drug scheduling on normalization benefit, we build a mathematical model that incorporates tumor growth, angiogenesis and IFP. We administer various theoretical combinations of antiangiogenic agents and cytotoxic nanoparticles through heterogeneous vasculature that displays a similar morphology to tumor vasculature. We observe differences in drug extravasation that depend on the scheduling of combined therapy; for concurrent therapy, total drug extravasation is increased but in adjuvant therapy, drugs can penetrate into deeper regions of tumor.
Year
DOI
Venue
2017
10.1371/journal.pcbi.1005724
PLOS COMPUTATIONAL BIOLOGY
Field
DocType
Volume
Tumor microenvironment,Drug Extravasation,Biology,Chemotherapy,Pharmacology,Targeted drug delivery,Adjuvant therapy,Angiogenesis,Drug,Drug delivery
Journal
13
Issue
Citations 
PageRank 
9
0
0.34
References 
Authors
2
5
Name
Order
Citations
PageRank
Sirin Yonucu100.34
Defne Yiotalmaz200.34
Colin Phipps310.73
Mehmet Burcin Unlu401.69
Kohandel Mohammad511.72