TITLE:
Combined Ang-2 and VEGF Targeting Therapies in Renal Cell Carcinoma
AUTHORS:
Nikolett Molnar, Dietmar W. Siemann
KEYWORDS:
Angiopoietin-2; Angiogenesis; Anti-Angiogenic Agent; Combination Therapy; Vascular Endothelial Growth Factor
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.4 No.9B,
September
30,
2013
ABSTRACT: Angiogenesis, the growth of new
vessels from pre-existing ones, is an important feature of tumor growth that
has been exploited as a therapeutic target in oncology. Given its key role in
facilitating blood vessel sprouting, VEGF has been a major focus of
anti-angiogenic strategies, but the observation of resistance in some clinical trials utilizing such
agents has led to a search for new or complementary targets in angiogenesis
process. The Angiopoietin/Tie2 pathway and in particular the Angiopoietin-2
(Ang-2) ligand which is critically involved in the destabilization of normal
vasculature, has been identified as one such target. The current study
investigated the potential benefits of combining an Ang-2 targeted therapy with
small molecule VEGF targeted agents (Sunitinib, Cediranib) in a human renal
cell carcinoma model. The results showed that while both Ang-2 and VEGF
interference on their own impaired tumor growth and new blood vessel formation,
the combination of agents that targeted both pathways resulted in significantly
superior anti-tumor and anti-angiogenic effects.