ScienceVEGF

Understanding tumour progression

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Important differences among antitumour strategies

In light of the proposed ongoing effects of VEGF inhibition, it is important to consider the possible reasons for tumour progression, which may vary widely among different antitumour strategies. With agents that target the tumour directly, progression often occurs through mutational pathways, in which tumour cells that are less sensitive to therapy emerge and repopulate the tumour. As a result, the effectiveness of many tumour-targeting agents may diminish over time.^7,12

 

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With agents that target VEGF directly, tumour progression may develop through non-mutational pathways. Based on preclinical observations, it has been proposed that endothelial cells and VEGF are genetically stable.⁹ Therefore, escape from agents that directly target VEGF is generally not thought to occur through acquired resistance but rather through the activation of secondary pathways. Activation of these redundant pathways may occur as a compensatory response to treatment or as a result of tumour cell mutations (i.e. mutations that are not associated with direct VEGF inhibition).^12–16 Because VEGF remains the predominant mediator of angiogenesis, one option to consider as tumours progress is to maintain precise VEGF inhibition and supplement it by selectively targeting other emergent pathways.^12,16