In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 6 ( 2021-6-2), p. e0252233-
Abstract:
Tumor angiogenesis is critical for the growth and progression of cancer. As such, angiostasis is a treatment modality for cancer with potential utility for multiple types of cancer and fewer side effects. However, clinical success of angiostatic monotherapies has been moderate, at best, causing angiostatic treatments to lose their early luster. Previous studies demonstrated compensatory mechanisms that drive tumor vascularization despite the use of angiostatic monotherapies, as well as the potential for combination angiostatic therapies to overcome these compensatory mechanisms. We screened clinically approved angiostatics to identify specific combinations that confer potent inhibition of tumor-induced angiogenesis. We used a novel modification of the ex ovo chick chorioallantoic membrane (CAM) model that combined confocal and automated analyses to quantify tumor angiogenesis induced by glioblastoma tumor onplants. This model is advantageous due to its low cost and moderate throughput capabilities, while maintaining complex in vivo cellular interactions that are difficult to replicate in vitro . After screening multiple combinations, we determined that glioblastoma-induced angiogenesis was significantly reduced using a combination of bevacizumab (Avastin®) and temsirolimus (Torisel®) at doses below those where neither monotherapy demonstrated activity. These preliminary results were verified extensively, with this combination therapy effective even at concentrations further reduced 10-fold with a CI value of 2.42E-5, demonstrating high levels of synergy. Thus, combining bevacizumab and temsirolimus has great potential to increase the efficacy of angiostatic therapy and lower required dosing for improved clinical success and reduced side effects in glioblastoma patients.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0252233
DOI:
10.1371/journal.pone.0252233.g001
DOI:
10.1371/journal.pone.0252233.g002
DOI:
10.1371/journal.pone.0252233.g003
DOI:
10.1371/journal.pone.0252233.g004
DOI:
10.1371/journal.pone.0252233.g005
DOI:
10.1371/journal.pone.0252233.t001
DOI:
10.1371/journal.pone.0252233.s001
DOI:
10.1371/journal.pone.0252233.s002
DOI:
10.1371/journal.pone.0252233.s003
DOI:
10.1371/journal.pone.0252233.s004
DOI:
10.1371/journal.pone.0252233.r001
DOI:
10.1371/journal.pone.0252233.r002
DOI:
10.1371/journal.pone.0252233.r003
DOI:
10.1371/journal.pone.0252233.r004
DOI:
10.1371/journal.pone.0252233.r005
DOI:
10.1371/journal.pone.0252233.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3