Soft tissue sarcomas of adults: state of the translational science.
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.
Borden
Ernest C
EC
The Cleveland Clinic Foundation, Cleveland, Ohio, 44195, USA. bordene@cc.ccf.org
Baker
Laurence H
LH
Bell
Robert S
RS
Bramwell
Vivien
V
Demetri
George D
GD
Eisenberg
Burton L
BL
Fletcher
Christopher D M
CD
Fletcher
Jonathan A
JA
Ladanyi
Marc
M
Meltzer
Paul
P
O'Sullivan
Brian
B
Parkinson
David R
DR
Pisters
Peter W T
PW
Saxman
Scott
S
Singer
Samuel
S
Sundaram
Murali
M
van Oosterom
Allan T
AT
Verweij
Jaap
J
Waalen
Jill
J
Weiss
Sharon W
SW
Brennan
Murray F
MF
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*