Ribonucleotide reductase as a novel target in liposarcoma

Rula Geha, M.D,  Memorial Sloan Kettering Cancer Center
Recipient of the: $25,000 Close Family Research Award

Advanced liposarcoma has low overall response rates to chemotherapy. There is a need for targeted therapy for liposarcoma. Utilizing microarray and RT-PCR data, we found ribonucleotide reductase M2 (RRM2) to be upregulated in our liposarcoma cell lines and tumor samples. Triapine, (3-Aminopyridine-2-carboxaldehyde-thiosemicarbazone) and hydroxyurea are ribonucleotide reductase inhibitors that exhibit anti-proliferative activity in epithelial and hematological malignancies. We have an attenuated herpes simplex virus that requires host cell ribonucleotide reductase to replicate. We hypothesize that RRM2 is a novel target for both chemotherapeutic agents and biological viral agents in the treatment of liposarcoma and plan to validate in the laboratory RRM2 as a new target for the treatment of liposarcoma.