title: Soft tissue sarcomas of adults: state of the translational science.
abstract: Sarcomas--like leukemias, which are also mesodermal malignancies--carry biological significance disproportionate to their clinical frequency. Identification of mutations and translocations associated with these tumors has illuminated aberrant signaling pathways that cause these diseases, determine their behavior, and are therapeutic targets. Activated receptor-associated tyrosine kinase c-kit, mutated in most gastrointestinal stromal tumors, has proven a clinically effective target for enzyme inhibition. A translocation involving a single gene family, consisting of EWS and related genes, has been identified in five different sarcomas, and its chimeric protein products could prove similarly amenable to inhibitors. Resolution of the histopathological complexity is being aided by data from molecular and chromosomal characterization. Improvements in imaging, definition of prognostic factors, and surgical and radiotherapeutic treatment have resulted in improved local control. Continued progress will depend on further adapting the rapidly evolving technologies of genomics and proteomics. It will also depend upon accurate histopathological diagnosis based on validated reagents and consistent methodologies applied to adequate tissue samples derived from patients with complete clinical data. Finally, multicenter, coordinated trials, such as those that occurred with assessment of imatinib mesylate in metastatic gastrointestinal stromal tumors, will assure the most rapid reductions in morbidity and mortality.
authors.affiliation: The Cleveland Clinic Foundation, Cleveland, Ohio, 44195, USA. bordene@cc.ccf.org
authors.forename: Ernest C
authors.initials: EC
authors.lastname: Borden
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Baker
authors.forename: Robert S
authors.initials: RS
authors.lastname: Bell
authors.forename: Vivien
authors.initials: V
authors.lastname: Bramwell
authors.forename: George D
authors.initials: GD
authors.lastname: Demetri
authors.forename: Burton L
authors.initials: BL
authors.lastname: Eisenberg
authors.forename: Christopher D M
authors.initials: CD
authors.lastname: Fletcher
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Fletcher
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
authors.forename: Paul
authors.initials: P
authors.lastname: Meltzer
authors.forename: Brian
authors.initials: B
authors.lastname: O'Sullivan
authors.forename: David R
authors.initials: DR
authors.lastname: Parkinson
authors.forename: Peter W T
authors.initials: PW
authors.lastname: Pisters
authors.forename: Scott
authors.initials: S
authors.lastname: Saxman
authors.forename: Samuel
authors.initials: S
authors.lastname: Singer
authors.forename: Murali
authors.initials: M
authors.lastname: Sundaram
authors.forename: Allan T
authors.initials: AT
authors.lastname: van Oosterom
authors.forename: Jaap
authors.initials: J
authors.lastname: Verweij
authors.forename: Jill
authors.initials: J
authors.lastname: Waalen
authors.forename: Sharon W
authors.initials: SW
authors.lastname: Weiss
authors.forename: Murray F
authors.initials: MF
authors.lastname: Brennan
mesh_terms: D000328:Adult; D017024:Chemotherapy, Adjuvant; D002869:Chromosome Aberrations; D006801:Humans; D007621:Karyotyping; D020411:Oligonucleotide Array Sequence Analysis; D012186:Retroperitoneal Neoplasms / Q000628:therapy; D012509:Sarcoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*