Preclinical testing of PARP-inhibitor BMN 673 against sarcoma
To date, the efficacy of PARP-inhibitors against sarcomas has not been evaluated in vivo. We have xenograft models generated from patient tumors with BRCA-ness mutation signature, indicative of PARP-inhibitor sensitivity. We also have several sarcoma cell lines, which have mutations in the DNA-damage repair pathway, showing great sensitivity to PARP-inhibitors in vitro, as predicted. Since patients with sarcoma are in need of improved treatment options, the therapeutic potential of PARP inhibition should be more carefully assessed in vivo, using sarcoma xenograft models. In this study we plan to test the efficacy of the more potent PARP-inhibitor, BMN 673 in vivo.
For the experiments, we plan to evaluate efficacy in up to five sarcoma models, and we plan to use up to 120 immunodeficient mice. We are expecting minimum impact of the treatment on the animal welfare. The administration of the drug by oral gavage will be executed by trained technicians. Tumors will be grown subcutaneous so the mice will not develop systemic disease or metastases.
For the experiments, we plan to evaluate efficacy in up to five sarcoma models, and we plan to use up to 120 immunodeficient mice. We are expecting minimum impact of the treatment on the animal welfare. The administration of the drug by oral gavage will be executed by trained technicians. Tumors will be grown subcutaneous so the mice will not develop systemic disease or metastases.