Strategies and methodologies for identifying molecular targets in sarcomas and other tumors

Sarcomas are a heterogeneous group of tumors that respond poorly to conventional cytotoxic chemotherapy. Sarcomas possess specific molecular characteristics that exist because of unique somatic mutations, vital growth factor or growth factor receptor overexpression, or are critically dependent on host pathways. Currently these tumors are classified on the basis of their tissue of origin and histologic appearance. Gene expression and proteomic analysis of sarcomas may enable reclassification of these tumors and help predict their biologic behavior and devise common therapeutic strategies within a class. It may not be long before cDNA/protein expression profiling and karyotyping complement the current standard pathological evaluation of a newly diagnosed sarcoma, thereby helping the clinician pick targeted agent(s) relevant to the expression profile. The spectacular success of imatinib in patients with gastrointestinal stromal tumor demonstrates how molecular targeting can fulfill the promise of low toxicity and high response rates. Finding new targets, and learning how to use the current generation of targeting drugs in sarcoma, are urgent challenges. Therapeutic clinical trials with a host of new molecular-targeting agents are underway that will drive new paradigms in sarcoma therapeutics. Patients with refractory disease who currently have no viable therapeutic options may have options that open up with the advent of newer targeted approaches, converting their disease from an acute short-lived one to a chronic process with preservation of quality of life while receiving therapy.