title: Therapeutic pipeline for soft-tissue sarcoma.
abstract: BACKGROUND
  Soft-tissue sarcomas (STS) represent a heterogeneous group of malignant tumors originating from connective tissues. Over recent years, this heterogeneity has led to a molecular breakdown of STS and subsequent use of targeted agents in several molecularly defined subgroups. After the initial success of imatinib in gastrointestinal stromal tumors, several other compounds have shown promising activity in some but not all subgroups of sarcoma.
  
  
  METHODS
  This review discusses the rational and clinical results, when available, that support this subtype-directed approach. In the vast majority of cases, these agents have been tested only in patients with advanced disease; as chemotherapeutic agents are developed as non-histotype-specific therapies, they are not discussed here. The PubMed literature was searched using the terms 'sarcoma', 'angiogenesis', 'mTOR' and 'targeted agents'. Proceedings of the annual meeting of the American Society of Clinical Oncology as well as those of the Connective Tissue Oncology Society were also searched for relevant information.
  
  
  CONCLUSIONS
  Many agents are currently developed in a subtype-specific manner in STS and this represents a significant leap forward. However, much remains to be done to improve our understanding of the molecular biology of this heterogeneous group of diseases.
authors.affiliation: Département de Médecine, Centre Léon Bérard, 69008 Lyon, France. cassierp@hotmail.com
authors.forename: Philippe A
authors.initials: PA
authors.lastname: Cassier
authors.forename: Sana Intidhar
authors.initials: SI
authors.lastname: Labidi-Galy
authors.forename: Pierre
authors.initials: P
authors.lastname: Heudel
authors.forename: Aurélie
authors.initials: A
authors.lastname: Dutour
authors.forename: Pierre
authors.initials: P
authors.lastname: Méeus
authors.forename: Maria
authors.initials: M
authors.lastname: Chelghoum
authors.forename: Laurent
authors.initials: L
authors.lastname: Alberti
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ray-Coquard
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors; D007335:Insulin-Like Growth Factor II / Q000037:antagonists & inhibitors; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors; D012509:Sarcoma / Q000188:drug therapy*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010982:Platelet-Derived Growth Factor; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; C546842:MTOR protein, human; D011505:Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1; D051058:Oncogene Protein v-akt; D058570:TOR Serine-Threonine Kinases