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New Therapeutic Targets in Soft Tissue Sarcoma

Demicco, Elizabeth G. MD, PhD*,†; Maki, Robert G. MD, PhD; Lev, Dina C. MD†,§; Lazar, Alexander J. MD, PhD*,†

Advances in Anatomic Pathology: May 2012 - Volume 19 - Issue 3 - p 170–180
doi: 10.1097/PAP.0b013e318253462f
Review Articles

Soft tissue sarcomas are an uncommon and diverse group of more than 50 mesenchymal malignancies. The pathogenesis of many of these is poorly understood, but others have begun to reveal the secrets of their underlying mechanisms. With considerable effort over recent years, soft tissue sarcomas have increasingly been classified on the basis of underlying molecular alterations. In turn, this has allowed the development and application of targeted agents in several specific, molecularly defined, sarcoma subtypes. This review will focus on the rationale for targeted therapy in sarcoma, with emphasis on the relevance of specific molecular factors and pathways in both translocation-associated sarcomas and in genetically complex tumors. In addition, we will address some of the early successes in sarcoma-targeted therapy as well as a few challenges and disappointments in this field. Finally, we will discuss several possible opportunities represented by poorly understood, but potentially promising new therapeutic targets, as well as several novel biological agents currently in preclinical and early phase I/II trials. This will provide the reader with the context for understanding the current state of this field and a sense of where it may be headed in the coming years.

Departments of *Pathology

§Cancer Biology

Sarcoma Research Center, The University of Texas M.D. Anderson Cancer Center, Houston, TX

Department of Hematology-Oncology, Mount Sinai School of Medicine, New York, NY

The authors have no funding or conflicts of interest to disclose.

Reprints: Alexander J. Lazar, MD, PhD, Department of Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0085, Houston, TX 77030-4009 (e-mail: alazar@mdanderson.org).

© 2012 Lippincott Williams & Wilkins, Inc.