Translating gene expression into clinical care: sarcomas as a paradigm.
Whereas most solid tumors are characterized by considerable genetic instability and molecular heterogeneity, sarcomas include many subtypes with very specific underlying molecular events driving oncogenesis. Gene expression profiling and other modern techniques have consequently had particular success in identifying the critical biologic pathways active in specific sarcomas, yielding insights which can be translated into useful diagnostic biomarkers. Public availability of data sets and new sequencing-based technologies will accelerate this process. Molecular studies have also identified oncogenic pathways of particular importance in sarcomas which can be targeted by investigational drugs. Examples include histone deacetylases in translocation-associated sarcomas of young adults, Akt/mammalian target of rapamycin in pleomorphic sarcomas, and macrophage colony-stimulating factor in tenosynovial giant cell tumor. Despite challenges in organization and accrual, future clinical trials of sarcomas need to be designed that take into account specific molecular subtypes as distinct diseases.
Nielsen
Torsten O
TO
Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada. torsten@interchange.ubc.ca
West
Robert B
RB
D016503:Drug Delivery Systems; D020869:Gene Expression Profiling; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors; D015514:Oncogene Proteins, Fusion / Q000037:antagonists & inhibitors; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012509:Sarcoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
D047908:Intracellular Signaling Peptides and Proteins; D015514:Oncogene Proteins, Fusion; D007334:Insulin-Like Growth Factor I; D016173:Macrophage Colony-Stimulating Factor; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases