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Table 1 Targeted therapy clinical studies for soft tissue sarcoma (STS)

From: Enhancer of zeste homolog 2 (EZH2) in pediatric soft tissue sarcomas: first implications

Biological molecular agents Molecular target(s) Clinical studies (phase) and clinical efficiency Reference
Tyrosine kinase inhibitors (TKIs)    
Imatinib mesylate (IM) c-Kit, PDGFR Phase II study: 53.7% of patients with GISTs showed a partial response, 27.9% of patients showed stable disease, 13.6% of patients showed early resistance to imatinib, 5% of patients showed serious adverse events [60]
   Phase III study: confirmation of the effectiveness of imatinib as primary systemic therapy for patients with incurable GIST. No advantages to higher dose treatment were reported. [61]
Sunitinib malate (SM) VEGF-R1, VEGF-R2, VEGF-R3, c-Kit, PDGFR, Flt-3, CSF1, neurotrophic factor receptors Phase III study: 7% of patients with GIST showed partial response, 58% had stable disease, 19% had progressive disease; 27.3 weeks was the time-to-tumor progression for sunitinib vs 6.4 weeks for placebo. Progression-free survival was similar. [62]
   Phase II study: 3-month progression-free rate of >40% for liposarcomas leiomyosarcomas [63]
   Phase II study: 52% of patients showed metabolic stable disease, 20% of patients achieved stable disease for at least 16 weeks, 47% of patients achieved partial response [64]
   Phase II study (current): SM activity in patients with certain subtypes of STS. The majority of these patients showed stable disease for 16 weeks. [65]
Sorafenib VEGF-R2, VEGF-R3, c-Kit, PDGFR, Raf/Mek/Erk Phase II study: 14% of patients with angiosarcoma and 6% of patients with leiomyosarcoma had a response, 64% of patients developed intolerance at the drug dose used [66]
   Phase II study: 78% patients with vascular tumors showed disease stabilization [67]
   Phase II study (current): antitumor activity and acceptable toxicity profile in patients with antracycline-refractory STS [68]
Pazopanib VEGF-Rs Phase II study: 12-week progression-free survival was reached by 44% patients with leiomyosarcoma, 49% of patients with synovial sarcomas, and 39% of patients with the other STS types [69]
Nilotinib BCR/ABL, c-Kit, PDGFR, CSF1R Phase I study: nilotinib alone or in combination with imatinib was well tolerated and showed clinical activity in imatinib-resistant GIST patients [70]
Mammalian target of rapamycin (mTOR) inhibitors    
Tensirolimus mTOR Phase II study: moderate toxicity and limited clinical activity [71]
Everolimus mTOR Phase II study: acceptable toxicity. Limited clinical activity in heavily pretreated patients with bone and soft tissue sarcomas. The efficacy in imatinib-refractory and sunitinib-refractory GIST is promising. [72]
Ridaforolimus (AP23573) mTOR Phase I study: safety of the drug; 27% of patients showed stable disease. [73]
   Phase II study: 29% of clinical benefit rate. Prolongation of survival. [74]
   Phase III study (current) [75]
Insulin-like growth factor (IGF) receptor antibodies    
Figitumumab IGF-1R Phase I study: good tolerance of the drug [76]
R1507 IGF-1R Phase II study (current): R1507 is well tolerated. Significant activity has been observed in Ewing's sarcoma, RMS and OS with several dramatic responses seen in Ewing's sarcoma and RMS. [77]
AMG479 IGF-1R Phase I study: absence of severe toxicities [78]
Mk-0646 IGF-1R Phase I study (current) [79]
  1. CSF1 = colony stimulating factor 1; Flt = fms-related tyrosine kinase; GIST = gastrointestinal stromal tumor; OS = osteosarcoma; PDGFR = platelet-derived growth factor receptor; RMS = rhabdomyosarcoma; VEGF = vascular endothelial growth factor.