Sunitinib in advanced alveolar soft part sarcoma: evidence of a direct antitumor effect

Ann Oncol. 2011 Jul;22(7):1682-1690. doi: 10.1093/annonc/mdq644. Epub 2011 Jan 17.


Background: The purpose of this study was to confirm sunitinib activity in alveolar soft part sarcoma (ASPS) and to report on new insights into the molecular bases thereof.

Patients and methods: From July 2007, nine patients with progressive metastatic ASPS received sunitinib 37.5 mg/day, within a named use program. Cryopreserved material was available for five naive patients, among whom three received sunitinib. Immunofluorescence (IF)/confocal microscopy, biochemical, and molecular/cytogenetic analyses were carried out, complemented by antiproliferative and activation assays in a short-term culture derived from one case.

Results: All patients were eligible for response. Best RECIST response was partial response in five cases, stable disease in three, and progression in one. The median progression-free survival was 17 months. Positron emission tomography results were consistent. Two cases of interval progressions were recorded. Antiproliferative assays and biochemistry on short-term culture showed that sunitinib is able to markedly impair ASPS cells growth and switch-off PDGFRB. IF/confocal microscopy demonstrated coexpression and physical association between PDGFRB/vascular endothelial growth factor receptor 2 (VEGFR2) and RET/VEGFR2 in ASPS cells, which was validated by biochemistry. PDGFRB, RET, and MET ligand-dependent activation was confirmed.

Conclusions: We confirm the clinical efficacy of sunitinib in ASPS, mediated by PDGFRB, VEGFR2, and RET, which are all expressed in tumor cells. A direct antitumor effect was shown in a short-term cell culture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Agents / therapeutic use*
  • Blotting, Western
  • Cell Proliferation / drug effects*
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Immunoprecipitation
  • In Situ Hybridization, Fluorescence
  • Indoles / therapeutic use*
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins c-ret / genetics
  • Proto-Oncogene Proteins c-ret / metabolism
  • Pyrroles / therapeutic use*
  • Receptor, Platelet-Derived Growth Factor beta / antagonists & inhibitors
  • Receptor, Platelet-Derived Growth Factor beta / genetics
  • Receptor, Platelet-Derived Growth Factor beta / metabolism
  • Retrospective Studies
  • Sarcoma, Alveolar Soft Part / drug therapy*
  • Sarcoma, Alveolar Soft Part / genetics
  • Sarcoma, Alveolar Soft Part / metabolism
  • Sunitinib
  • Survival Rate
  • Treatment Outcome
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism
  • Young Adult


  • Antineoplastic Agents
  • Indoles
  • Pyrroles
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • Receptor, Platelet-Derived Growth Factor beta
  • Vascular Endothelial Growth Factor Receptor-2
  • Sunitinib