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[Molecular biology of sarcoma and therapeutic choices].

Abstract
Soft tissue sarcomas (STS) are a set of very heterogeneous tumors with numerous histological categories. The development of the molecular biology allowed identifying recurring molecular anomalies in certain subgroups of sarcomas, being able to represent diagnostic, prognosis and therapeutic tools. The molecular classification of STS includes until today 5 main groups of abnormalities: sarcomas with "simple genomic profile" showing reciprocal (1) chromosomal translocations, (2) activating mutation, (3) inhibitive mutation or (4) simple amplification; (5) sarcomas with "complex genomic profile" can include several tens of molecular abnormalities. The development of new-targeted therapies is based on the identification of a target, specific of a tumors subgroup and involved in carcinogenesis mechanisms and/or tumoral growth. Then, the aim of clinical research is to establish the proof of the concept through clinical trials, demonstrating the benefit brought to the patient and ending in the marketing of the drug. This proof of the concept was clearly established for imatinib, sunitinib and regorafenib in gastrointestinal stromal tumors, for imatinib in dermatofibrosarcoma protuberans and pigmented vilo-nodular synovitis, for denosumab in giant cell tumors of the bone, ending in the authorization to use these new therapies in these indications. It is in progress and promising for anti-IGF-1R in Ewing sarcomas, for crizotinib in myofibroblastic inflammatory tumors, for mTOR inhibitor in PEComas... The role of molecular abnormalities identified in the mechanisms of tumoral progress for sarcomas and their potential therapeutic impact will be detailed.
AuthorsArmelle Dufresne, Philippe Cassier, Pierre Heudel, Daniel Pissaloux, Qing Wang, Jean-Yves Blay, Isabelle Ray-Coquard
JournalBulletin du cancer (Bull Cancer) Vol. 102 Issue 1 Pg. 6-16 (Jan 2015) ISSN: 1769-6917 [Electronic] France
Vernacular TitleBiologie moléculaire des sarcomes et choix thérapeutiques.
PMID25609490 (Publication Type: Journal Article, Review)
CopyrightCopyright © 2015. Published by Elsevier Masson SAS.
Chemical References
  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Benzamides
  • Indoles
  • Phenylurea Compounds
  • Piperazines
  • Pyrazoles
  • Pyridines
  • Pyrimidines
  • Pyrroles
  • regorafenib
  • Denosumab
  • Crizotinib
  • Imatinib Mesylate
  • Sunitinib
Topics
  • Angiogenesis Inhibitors (therapeutic use)
  • Antibodies, Monoclonal, Humanized (therapeutic use)
  • Benzamides (therapeutic use)
  • Bone Neoplasms (genetics, therapy)
  • Crizotinib
  • Denosumab
  • Dermatofibrosarcoma (genetics, therapy)
  • Gastrointestinal Stromal Tumors (genetics, therapy)
  • Gene Amplification
  • Gene Deletion
  • Giant Cell Tumor of Bone (genetics, therapy)
  • Humans
  • Imatinib Mesylate
  • Indoles (therapeutic use)
  • Molecular Targeted Therapy
  • Phenylurea Compounds (therapeutic use)
  • Piperazines (therapeutic use)
  • Point Mutation
  • Prognosis
  • Pyrazoles (therapeutic use)
  • Pyridines (therapeutic use)
  • Pyrimidines (therapeutic use)
  • Pyrroles (therapeutic use)
  • Sarcoma (classification, genetics, therapy)
  • Sarcoma, Ewing (genetics, therapy)
  • Sunitinib
  • Synovitis, Pigmented Villonodular (genetics, therapy)
  • Translocation, Genetic

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