title: Emerging therapeutic targets for synovial sarcoma.
abstract: Synovial sarcoma is part of soft tissue sarcomas, an uncommon group of malignant tumors of mesenchymal origin. Unfortunately, a very limited number of useful drugs are active for most advanced synovial sarcoma. These tumors showed VEGF expression, and elevated serum VEGF levels correlate with higher histologic tumor grade. Inhibition of VEGFR was associated with tumor activity in preclinical models of synovial sarcoma and drugs such as sorafenib, pazopanib and bevacizumab have been employed in synovial sarcoma in monotherapy and in combination with chemotherapy. Other targets such as EGFR, HER2, IGFR-1R and mTOR have been exploited, but their inhibition by drugs such as gefitinib, trastuzumab, figitumumab, and temsirolimus, has not resulted in meaningful activity. Newer approaches include CXCR4 inhibition, immune-based therapies (NY-ESO-1), targeting epigenetic misregulation with HDAC inhibitors and targeting developmental pathways such Notch and Hedgehog. This review will summarize achievements and pitfalls of drugs against emerging therapeutic targets for synovial sarcoma.
authors.affiliation: Chemotherapy, Musculoskeletal Oncology, Istituto Ortopedico Rizzoli, Bologna, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Palmerini
authors.forename: Anna
authors.initials: A
authors.lastname: Paioli
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000068258:Bevacizumab / Q000494:pharmacology / Q000627:therapeutic use; D000068338:Everolimus / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007191:Indazoles; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D058990:Molecular Targeted Therapy / Q000379:methods*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D012509:Sarcoma / Q000188:drug therapy; D013584:Sarcoma, Synovial / Q000188:drug therapy* / Q000378:metabolism; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000077157:Sorafenib; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D000077210:Sunitinib; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D009536:Niacinamide; D000068258:Bevacizumab; C515074:ridaforolimus; C401859:temsirolimus; C516667:pazopanib; D000068338:Everolimus; D000077157:Sorafenib; C546842:MTOR protein, human; D040262:Receptors, Vascular Endothelial Growth Factor; D058570:TOR Serine-Threonine Kinases; D000077210:Sunitinib; C525021:figitumumab; D020123:Sirolimus
keywords: CXCR4; HDAC inhibitors; IGFR-1R; NY-ESO-1; VEGFR; mTOR; notch; soft tissue sarcoma; synovial sarcoma; therapeutic targets