| Abstract: |
Great insights into the molecular mechanisms that lead to the formation of sarcomas have been gained over the last decade. The fusion products inherent to certain subtypes of sarcomas have been cloned, and their mechanisms of action are currently being elucidated. Similarly, much progress has been made in the understanding of signal transduction cascades that are dysregulated in sarcomas. In both these cases advancements are already contributing to clinical practice. However, much more remains to be learned for the translocation-specific sarcomas, and those with identifiable signal transduction cascade abnormalities make up only a small percentage of the 10,000 patients with newly diagnosed sarcomas presenting for recommendations for treatment options in the United States annually. It is hoped that as the molecular targets are better elucidated that more people with a variety of sarcomas will have the benefit observed with imatinib in patients with GIST and dermatofibrosarcoma protuberans. Most notably absent from this review is any discussion of leiomyosarcoma (LMS) and malignant fibrous histiocytoma (MFH, now termed "undifferentiated high grade pleomorphic sarcoma" in the latest fascicle from the World Health Organization), as well as osteogenic sarcoma and conventional chondrosarcoma, two of the most common sarcomas of soft tissue and bone, respectively. The lack of discussion about these sarcoma subtypes is a reflection on our current understanding of their biology. As a case in point, LMS includes uterine LMS (often grouped under "uterine cancer"), as well as LMS that arise in the retroperitoneum or extremity. All are pathologically indistinguishable, yet they have distinct clinical behaviors and respond differently to chemotherapy. The molecular basis for these distinctions is unclear. In LMS, it is believed that differentiating smooth muscle cells are the precursors, whereas in the case of MFH even the precursor cells are unknown. In conclusion, although many more details remain to be elucidated, the hope is that the knowledge that has been obtained from the study of better characterized sarcomas will be applicable to more common aneuploid sarcomas, as well as to solid tumors as a whole. Progress at the laboratory bench in this rare and unusual group of cancers will result in an acceleration of treatments for these and more common cancers at the patient's bedside. © 2005 Elsevier Inc. All rights reserved. |
