This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Osteosarcoma is the most common malignant bone tumor in children. Although the introduction of adjuvant chemotherapy two decades ago dramatically improved survival, over the last 20 years survival has not improved significantly. In recent studies early response of cancer to treatment has been shown to be the strongest prognostic factor. However in osteosarcoma no biomarkers are available to measure the early response to treatment. Attempts to intensify therapy after surgery after 12 weeks of therapy for patients with a poor response have not improved outcomes. Therefore efforts to improve outcomes will require the preoperative use of more intensive chemotherapy or new agents for all patients, which would result in an increased risk of toxicities for patients that could be cured with just standard chemotherapy. In spite of the widely appreciated magnitude of this problem there are currently no diagnostic tools that measure the early response to treatment in osteosarcoma. Proteins are logical candidates to use as biomarkers in cancer for evaluating disease response and developing new treatments. Surface enhanced laser desorption/ionization time of flight (SELDI-TOF) mass spectrometry is a recently developed technique that allows for the simultaneous analysis of multiple proteins from serum. It has been used successfully to establish distinct serum protein profiles for ovarian, breast, and prostate cancer. As part of the Children's Oncology Group osteosarcoma biology protocol, serum was collected and stored frozen on all patients at the time of diagnosis and is used to establish the distinctive serum protein profiles of patients with osteosarcoma. The protocol for serum protein profiling of osteosarcoma samples was reviewed and approved by the Children's Oncology Group, and it has made all its samples available. However no serum was collected during chemotherapy treatment or relapse monitoring on this protocol. Therefore this pilot study is designed to prospectively collect serum from osteosarcoma patients to be able to construct a link between serum biomarkers and the response to chemotherapy and to evaluate the use of these biomarkers for early relapse detection. The serum samples collected locally will also be used to verify that the pattern found on serum samples obtained by the Children's Oncology Group is reproducible and specific for osteosarcoma. The serum samples will be analyzed by the surface enhanced laser desorption/ionization time of flight (SELDI-TOF) mass spectrometry. The analysis will be done with a bioinformatic tool based on the genetic algorithm and a cluster analysis method.
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