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The all too common development of resistance to therapy is a major obstacle to successful cancer treatment. Therefore understanding the mechanisms by which tumours become insensitive to a given treatment is a key to identifying new drugs or adjuvant therapies. These two related projects from Dr. Cornelius Boerkoel seek to exploit the discovery that a mutation in the DNA repair enzyme tyrosyl – DNA phosphodiesterase?1 (Tdp1) sensitizes tumour cells to the cytotoxic effects of toxic agents such as camptothecin (CPT) and radiation therapy. The projects goal was to find pharmacological inhibitors of Tdp1 as potential adjuvants to these frontline therapies. Screening efforts at CDRD have identified several small molecule inhibitors of Tdp1. None of the compounds identified showed improved activity over compounds already in hand. In addition, the animal study results were inconclusive. As the project did not meet its endpoint it has been returned back to the investigator for further research.