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Soft Tissue Sarcomas of Adults

State of the Translational Science¹

The Cleveland Clinic Foundation, Cleveland, Ohio [E. C. B.]; University of Michigan, Ann Arbor, Michigan [L. H. B.]; Princess Margaret Hospital, Toronto, Ontario, Canada [R. S. B., B. O.]; London Regional Cancer Centre, London, Ontario, Canada [V. B.]; Dana-Farber Cancer Institute, Boston, Massachusetts [G. D. D.]; Fox Chase Cancer Center, Philadelphia, Pennsylvania [B. L. E.]; Brigham and Women’s Hospital, Boston, Massachusetts [C. D. M. F., J. A. F.]; Memorial Sloan-Kettering Cancer Center, New York, New York [M. L., S. Si., M. F. B.]; National Human Genome Research Institute, Bethesda, Maryland [P. M.]; Novartis Pharmaceuticals, East Hanover, New Jersey [D. R. P., P. W. T. P.]; National Cancer Institute, Bethesda, Maryland [S. Sa.]; Mayo Clinic, Rochester, Minnesota [M. S.]; Universitaire Ziekenhuizen Gasthuisberg, Leuven, Belgium [A. T. v. O.]; Erasmus University Medical Center, Rotterdam, the Netherlands [J. V.]; The Scripps Research Institute, La Jolla, California [J. W.]; and Emory University, Atlanta, Georgia [S. W. W.]

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.

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