Site Search:

Cisplatin, doxorubicin, and high-dose methotrexate are chemotherapeutic drugs often used to treat osteosarcoma. Why some tumor cells exhibit resistance to these drugs is unknown.

We are testing the hypothesis that chemotherapy-induced tumor death releases molecules from the dying osteosarcoma cells that act to protect some of the remaining tumor cells, allowing the survivor tumor cells to continue growing. We are presently studying the capacity of a protein known as high mobility group box 1 (HMGB1) to protect osteosarcoma cells from cisplatin.

HMGB1 is a protein that is found in nearly all cells and is involved in turning genes off and on. However, outside the cell it takes on other roles, one of which appears to be related to tumor growth and metastasis, although its mechanism of action remains unknown. We have discovered that both normal bone cells and some osteosarcoma cells release HMGB1 and our preliminary data suggest that this release protects some bone tumor cells from cisplatin treatment.

We are currently in the process of determining whether serum HMGB1 can be used as a biomarker for following patient response to chemotherapy. HMGB1 levels will be analyzed in serum samples obtained from patients involved in clinical trials at Riley Hospital for Children that will provide an HMGB1 profile throughout treatment and recovery.