Cancer de mama

reviews antiangiogenic clinical strategies

Biomarkers of response and resistance to antiangiogenic therapy
Rakesh K. Jain, Dan G. Duda, Christopher G. Willett, Dushyant V. Sahani, Andrew X. Zhu, Jay S. Loeffler, Tracy T. Batchelor and A. Gregory Sorensen abstract | 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.
Jain, r. K. et al. Nat. Rev. Clin. Oncol. 6, 327–338 (2009); doi:10.1038/nrclinonc.2009.63

Introduction

tumors acquire blood vessels by co-option of neighboring vessels, from sprouting or intussusceptive microvascular growth and by vasculogenesis from endothelial precursor cells.1 in most solid tumors the newly formed vessels are plagued by structural and functional abnormalities owing to the sustained