S Stacchiotti1, T Negri2, N Zaffaroni3, E Palassini4, C Morosi5, S Brich2, E Conca2, F Bozzi2, G Cassinelli3, A Gronchi6, P G Casali4, S Pilotti2. 1. Department of Cancer Medicine. Electronic address: silvia.stacchiotti@istitutotumori.mi.it. 2. Department of Pathology, Laboratory of Experimental Molecular Pathology. 3. Department of Experimental Oncology and Molecular Medicine. 4. Department of Cancer Medicine. 5. Department of Radiology. 6. Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Abstract
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.
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.
Authors: Gabriel G Malouf; Guillaume Beinse; Julien Adam; Olivier Mir; Ali N Chamseddine; Philippe Terrier; Charles Honore; Jean-Philippe Spano; Antoine Italiano; Jean-Emmanuel Kurtz; Jean-Michel Coindre; Jean-Yves Blay; Axel Le Cesne Journal: Oncologist Date: 2019-01-09
Authors: Silvia Stacchiotti; Olivier Mir; Axel Le Cesne; Bruno Vincenzi; Alexander Fedenko; Robert G Maki; Neeta Somaiah; Shreyaskumar Patel; Mehedi Brahmi; Jean Y Blay; Kjetil Boye; Kirsten Sundby Hall; Hans Gelderblom; Nadia Hindi; Javier Martin-Broto; Hanna Kosela; Piotr Rutkowski; Antoine Italiano; Florence Duffaud; Eisuke Kobayashi; Paolo G Casali; Salvatore Provenzano; Akira Kawai Journal: Oncologist Date: 2017-07-28
Authors: Patricia L Zadnik; Alp Yurter; Rosa DeLeon; Camilo A Molina; Mari L Groves; Edward McCarthy; Daniel M Sciubba Journal: Skeletal Radiol Date: 2013-10-04 Impact factor: 2.199