Understanding and targeting resistance to anti-angiogenic therapies - PubMed (original) (raw)

Understanding and targeting resistance to anti-angiogenic therapies

Jeffrey M Clarke et al. J Gastrointest Oncol. 2013 Sep.

Abstract

Therapies targeting tumor angiogenesis are used in a variety of malignancies, however not all patients benefit from treatment and impact on tumor control may be transient and modest. Mechanisms of resistance to anti-angiogenic therapies can be broadly categorized into VEGF-axis dependent alterations, non-VEGF pathways, and stromal cell interactions. Complimentary combinations of agents that inhibit alternative mechanisms of blood vessel formation may optimize inhibition of angiogenesis and improve clinical benefit for patients. The purpose of this review is to detail the preclinical evidence for mechanisms of angiogenic resistance and provide an overview of novel therapeutic approaches exploiting these pathways.

Keywords: Cancer; VEGF; angiogenesis; colorectal cancer; resistance; vascular endothelial growth factor.

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Figures

Figure 1

VEGF-axis dependent and non-VEGF mediated mechanisms of resistance to anti-angiogenic therapies. Non-VEGF axis receptors include TGF-β receptor, Tie2, PDGFR, FGFR, and Dll4-Notch. General mechanisms of action for ziv-Aflibercept, bevacizumab, ramucirumab, and VEGFR activity of RTK inhibitors are depicted. Novel targeted therapies include TRC105, PF-03446962, LY2157299, demcizumab, MEDI0639, and RGN-421 inhibiting TGF-β and Dll4-Notch signaling

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