LAUSR

Cancers are characterized by high levels of genomic instability and endogenous DNA damage. Traditional cancer therapies include radiotherapy and DNA-damaging chemotherapy, but these treatments are associated with significant damage to normal tissue. These unwanted side effects may be reduced by using targeted treatment approaches that preferentially affect tumor cells with specific mutations. The DNA damage response (DDR) in cancer cells differs in at least three aspects to those of normal cells, namely the loss of one or more DDR pathway or capability, increased levels of replication stress and higher levels of endogenous DNA damage. In addition, an analysis of DDR associated genes suggests that there are more than 450 gene products involved in various aspects of DDR, many of which are performing enzymatic activities that could be targeted by small molecule inhibitors. DDR therefore represents both a hallmark of cancer and a weakness that can be exploited for new cancer therapies. Both the opportunities and challenges associated with translating inhibitors of DDR into new medicines for cancer patients will be presented. Citation Format: Mark J. O9Connor. Targeting the DNA damage response to generate new medicines for cancer treatment [abstract]. In: Proceedings of the AACR Special Conference on DNA Repair: Tumor Development and Therapeutic Response; 2016 Nov 2-5; Montreal, QC, Canada. Philadelphia (PA): AACR; Mol Cancer Res 2017;15(4_Suppl):Abstract nr IA03.