The role of tumor microenvironment in resistance to anti-angiogenic therapy

F1000Res. 2018 Mar 15:7:326. doi: 10.12688/f1000research.11771.1. eCollection 2018.


Anti-angiogenic therapy has been demonstrated to increase progression-free survival in patients with many different solid cancers. Unfortunately, the benefit in overall survival is modest and the rapid emergence of drug resistance is a significant clinical problem. Over the last decade, several mechanisms have been identified to decipher the emergence of resistance. There is a multitude of changes within the tumor microenvironment (TME) in response to anti-angiogenic therapy that offers new therapeutic opportunities. In this review, we compile results from contemporary studies related to adaptive changes in the TME in the development of resistance to anti-angiogenic therapy. These include preclinical models of emerging resistance, dynamic changes in hypoxia signaling and stromal cells during treatment, and novel strategies to overcome resistance by targeting the TME.

Keywords: MET signaling; anti-angiogenic therapy; drug resistance; tumor microenvironment.

Publication types

  • Review