Preclinical testing Targeting BRCA-ness osteosarcomas with PARP inhibitor
A study by Baumhoer and co-workers in 2015 showed that many osteosarcomas have a mutation signature that suggests similarity to BRCA-deficient breast and ovarian cancer. Such “BRCA-ness” could indicate a deficiency in the homologous recombination repair (HRR) pathway, and suggests that PARP-inhibitors might have a therapeutic potential. The concept “synthetic lethality” is based on PARP-inhibitors inducing cell death in cancer cells with a deficient HRR pathway by blocking the alternative repair pathway, whilst normal cells can repair damage and remain viable. In this project we are combining the genomics approach with preclinical drug testing, and have found striking effect of PARP inhibition in osteosarcoma cells with defects in the HRR pathway. These studies are being taken further in our patient-derived mouse models.
