Biomarkers of response and resistance to antiangiogenic therapy

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Abstract
No validated biomarkers currently exist for appropriately selecting cancer patients for antiangiogenic therapy. A number of potential systemic, circulating, tissue and imaging biomarkers have emerged as suitable candidate biomarkers, but all require prospective validation. The authors discuss the current challenges in establishing biomarkers, the advantages and disadvantages of systemic, circulating, tissue and imaging biomarkers, and the future opportunities for validating biomarkers of antiangiogenic therapy. No validated biological markers (or biomarkers) currently exist for appropriately selecting patients with cancer for antiangiogenic therapy. Nor are there biomarkers identifying escape pathways that should be targeted after tumors develop resistance to a given antiangiogenic agent. A number of potential systemic, circulating, tissue and imaging biomarkers have emerged from recently completed phase I–III studies. Some of these are measured at baseline (for example VEGF polymorphisms), others are measured during treatment (such as hypertension, MRI-measured Ktrans, circulating angiogenic molecules or collagen IV), and all are mechanistically based. Some of these biomarkers might be pharmacodynamic (for example, increase in circulating VEGF, placental growth factor) while others have potential for predicting clinical benefit or identifying the escape pathways (for example, stromal-cell-derived factor 1α, interleukin-6). Most biomarkers are disease and/or agent specific and all of them need to be validated prospectively. We discuss the current challenges in establishing biomarkers of antiangiogenic therapy, define systemic, circulating, tissue and imaging biomarkers and their advantages and disadvantages, and comment on the future opportunities for validating biomarkers of antiangiogenic therapy.