Systemic therapy for advanced soft-tissue sarcomas.

The field of oncology is experiencing a paradigm shift from broad-spectrum cytotoxic therapies to more specific molecularly based targeted therapies. The activity of imatinib mesylate in chronic myelogenous leukemia and gastrointestinal stromal tumors (GIST) has reinforced our faith in translational research and its potential impact on the cure of cancer and improvement in quality of life for patients. This breakthrough has been particularly exciting for the field of sarcoma and for patients with advanced GIST, for whom no other effective therapy was available. Unfortunately, as is becoming increasingly clear, cancer is a very complex problem with multiple mechanisms and pathways that function either independently or interdependently enabling cell survival. We are therefore far away from having solved the problem. Attempts at refining the currently available therapeutic armamentarium to maximize the therapeutic index (dose intensification with growth factor support) must continue in parallel with laboratory-based research identifying critical targets to be inhibited or blocked. Identification of new agents with some activity, such as gemcitabine and ecteinascidin (ET-743), is also of paramount importance.