Dual inhibition of Ang-2 and VEGF receptors normalizes tumor vasculature and prolongs survival in glioblastoma by altering macrophages
Abstract
Inhibition of the VEGF/VEGF receptor (VEGFR) pathway has failed to increase overall survival in phase III trials in patients with glioblastoma (GBM). Previously we identified the angiopoietin-2 (Ang-2)/TEK receptor tyrosine kinase (Tie-2) pathway as a potential driver of resistance to VEGF inhibition in GBM. Here we show that dual inhibition of VEGFRs and Ang-2 inhibits tumor growth and prolongs vessel normalization compared with VEGFR inhibition alone, resulting in improved survival in murine GBM models. Furthermore, by blocking macrophage recruitment, we demonstrate that macrophages contribute to the beneficial effects of dual therapy.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 04, 2016
- Source ID
- 10.1073/pnas.1525349113
Entities
People
- Alona Muzikansky
- Ana Batista
- Ching Ching Leow
- Christian T Farrar
- Dai Fukumura
- Dan G Duda
- Giorgio Seano
- Jermaine Goveia
- Jonas Kloepper
- Keehoon Jung
- Koen A. Marijt
- Lei Xu
- Matija Snuderl
- Meenal Datta
- Nathaniel D. Kirkpatrick
- Rakesh Jain
- Sampurna Chatterjee
- Teresa E. Peterson
- Tracy T. Batchelor
- Trupti Vardam
- Walid S. Kamoun
- Yuhui Huang
- Zohreh Amoozgar
Organizations
- AstraZeneca (United States)
- Harvard Medical School
- Harvard University
- National Cancer Institute
- Tufts University
- United States Department of Defense