Pazopanib a tyrosine kinase inhibitor with strong anti-angiogenetic activity: a new treatment for metastatic soft tissue sarcoma

Crit Rev Oncol Hematol. 2014 Feb;89(2):322-9. doi: 10.1016/j.critrevonc.2013.08.012. Epub 2013 Sep 4.

Abstract

Soft tissue sarcomas (STS) are rare tumors with mesenchymal origin, accounting for 1% of all human cancer. Local control of STS can be obtained through the use of surgery and radiotherapy. In about 40% of these patients, disease will recur at distant sites, and of these more than 90% will die because of this aggressive malignancy. In advanced and/or metastatic STS patients treated with anthracycline-based regimen the median overall survival is about 12 months, and it has remained unchanged during the last 20 years. Clearly, this strongly suggests the need for discover more active compounds in STS, such as imatinib in GIST or dermatofibrosarcoma patients. In this paper we describe the crucial role of angiogenesis mechanisms in sarcomas development and progression. Consequentially, we focus on pazopanib, a novel multitargeted tyrosine kinase inhibitor with anti-angiogenic activity, mainly due to VEGFR2 pathway interference. We also analyze principal completed trials leading pazopanib approval in sarcomas pretreated patients.

Keywords: Angiogenesis; Pazopanib; Soft tissue sarcoma; Targeted therapy; Tyrosine kinase inhibitor (TKI); Vascular endothelial growth factor (VEGF).

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Humans
  • Indazoles
  • Molecular Targeted Therapy
  • Neoplasm Metastasis / drug therapy*
  • Neoplasm Metastasis / pathology
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use*
  • Sarcoma / drug therapy*
  • Sarcoma / metabolism
  • Sarcoma / pathology*
  • Signal Transduction / drug effects
  • Sulfonamides / pharmacology
  • Sulfonamides / therapeutic use*
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Angiogenesis Inhibitors
  • Indazoles
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Sulfonamides
  • pazopanib
  • Vascular Endothelial Growth Factor Receptor-2