Sunitinib malate and figitumumab in solitary fibrous tumor: patterns and molecular bases of tumor response
Authors: Elena Palassini
Elena Conca
Marco A Pierotti
Tiziana Negri
Ugo Pastorino
Alessandro Gronchi
Antonella Messina
Paolo G Casali
Carlo Morosi
Silvia Stacchiotti
Silvana Pilotti
Journal: Molecular Cancer Therapeutics (2010)
Discipline: CLINICAL MEDICINE
Keywords: Antiangiogenic treatment; Solitary fibrous tumor; Sunitinib malate; Receptor tyrosine kinase; Metastatic
Affiliations: Adult Sarcoma Medical Oncology Unit, Department of Cancer Medicine, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico Istituto Nazionale Tumori, Milan, Italy. 

Abstract:  Antiangiogenic treatment activity has been reported in solitary fibrous tumor (SFT), a rare and little chemosensitive sarcoma. We explored the activity of sunitinib malate (SM) in SFT and studied receptor tyrosine kinase (RTK) activation profile. Eleven patients with progressive metastatic SFT resistant to chemotherapy were treated with continuous-dosing 37.5 mg/d SM on a named-use basis. One of them also received the insulin-like growth factor I receptor (IGFIR) inhibitor figitumumab after developing secondary resistance to SM. Besides, biochemical, molecular, and fluorescence in situ hybridization analyses were done in eight na√Øve SFTs whose cryopreserved material was available to clarify RTK upstream and downstream signaling. In two cases treated with SM and belonging to the na√Øve series, both pretreatment and posttreatment samples were available. Ten patients were evaluable for response to SM. The best response according to the Choi criteria was six partial response (all with Response Evaluation Criteria in Solid Tumors stable disease), one stable disease, and three progressive disease. Responses lasted &gt;6 months in five patients. The eight na√Øve samples showed high expression/phosphorylation of PDGFRB, epidermal growth factor receptor, and IGFIR/IR, in the presence of their cognate ligands. Downstream pathways revealed expression/activation of Akt, extracellular signal-regulated kinase 1-2 and, closely related to SFT subtypes, of S6 and 4E-BP1. In two patients, whose pretreatment and posttreatment clinical and molecular status were available, biochemical data confirmed the activity of SM, although they also suggested a possible time-dependent shift of dominant RTK from PDGFRB to IGFIR/insulin receptor. A Response Evaluation Criteria in Solid Tumors partial response to figitumumab corroborated these findings. SM has antitumor activity in SFT, possibly through a PDGFRB-mediated mechanism, but treatments with IGFIR/insulin receptor and possibly epidermal growth factor receptor inhibitors are worth testing. 

Retracted: No

PubPeer comments:
 Figure 3D. * Datapoints in these two plots look more similar than expected. Some areas that look remarkably similar have been highlighted with rounded boxes of the same color.  , 
 Retracted [7 March 2022] . ------------------- The above article, published online on 7 June 2019 in Wiley Online Library has been retracted by agreement between the authors, the journal s Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed after the authors stated that unintentional errors occurred during the research process, and the experimental results cannot be verified. Thus, the conclusions are considered to be invalid. ,