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Biomarkers predicting tumor response and evasion to anti-angiogenic therapy
Authors:Arman JahangiriManish K Aghi
Institution:
  • Brain Tumor Research Center; University of California, San Francisco (UCSF) Department of Neurosurgery, USA
  • Abstract:No fully validated biological markers currently exist to predict responsiveness to or the development of evasion to anti-angiogenic therapy of cancer. The identification of such biomarkers is vital to move these therapies forward, as failure to respond to these treatments is often associated with rapid tumor progression that could have been averted had the intrinsic or acquired evasion to anti-angiogenic therapy been identified in a timely fashion. Furthermore, the high cost of antiangiogenic therapies makes it important to avoid utilizing them in the setting of lack of response or developing evasion, making the identification of biomarkers even more important. A number of potential physiologic, circulating, tissue, and imaging biomarkers have emerged from recently completed preclinical animal studies and clinical trials. In this review, we define 5 different types of biomarkers (physiologic, circulating, intratumoral, genetic polymorphisms, and radiographic); discuss the challenges in establishing biomarkers of antiangiogenic therapy in animal models and in clinical trials; and discuss future strategies to identify and validate biomarkers of anti-angiogenic therapy.
    Keywords:DBP  diastolic blood pressure  PFS  progression-free survival  OS  overall survival  VEGF  vascular endothelial growth factor  PIGF  Placental growth factor  VEGFR  vascular endothelial growth factor receptor  sVEGFR  soluble vascular endothelial growth factor receptor  (IL-6)  interleukin 6  IL-8  interleukin 8  EPCs  endothelial progenitor cells  CECs  circulating endothelial cells  CA9  carbonic anhydrase 9  HIF-1α  hypoxia-inducible factor-1α  KRAS  V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog  bFGF  basic fibroblast growth factor  sTie-2  angiopoietin receptor Tie-2  sVEGFR-1  soluble vascular endothelial growth factor rector 1  MMPs  matrix metalloproteinases  MCP-3  macrophage chemoattractant protein-3  DWI  diffusion weighted imaging  NSCLC  non-small cell lung cancer  HCC  hepatocellular carcinoma  RTKI  receptor tyrosine kinase inhibitor
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