Acquired tumor resistance to antiangiogenic therapy: Mechanisms at a glance

Bahare Zarin, Farzane Zarifi, Golnaz Vaseghi, Shaghayegh Haghjooy Javanmard


Angiogenesis is critical for oxygen and nutrient delivery to proliferating tumor cells. Th erefore, as angiogenesis is required and
vital for the tumor growth and metastasis. Antiangiogenic therapy is considered to be benefi cial for tumor growth prevention due
to starvation of tumor of oxygen and nutrients, but in some cases, the benefi ts are not permanent. Tyrosine kinase inhibitors and many other agents often target angiogenesis through inhibition of the vascular  ndothelial growth factor (VEGF) pathway. Although preclinical studies showed satisfactory outcomes in tumor growth inhibition, antiangiogenic therapy in the clinical setting may not be eff ective.Th e resistance  bserved in several tumor types through alternative angiogenic “escape” pathways contributes to restoration of tumor growth and may induce  rogression, enhancement of invasion, and metastasis. Th erefore,   tivation of major compensatory angiogenic pathways, sustaining tumor angiogenesis during VEGF blockade contributing to the recurrence of tumor
growth overcome antiangiogenic strategies. In this review, we summarize the novel mechanisms involved in evasive resistance to antiangiogenic therapies and represent diff erent cancer types which have the ability to adapt to VEGF inhibition achieving resistance to antiangiogenic therapy through these adaptive mechanisms.


Angiogenesis inhibitors, antiangiogenic resistance, metastasis, tumor growth restoration

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