Targeting DNA damage repair pathway for pancreatic cancer therapy
With the development of immunotherapies and target therapy,the survival time has been extended in other cancers,however,the 5 years overall survival of pancreatic cancer patient remains below 10％.It is still a challenge for treatment pancreatic cancer and novel strategies are necessary to improve the therapeutic efficiency.DNA damage repair(DDR)system was developed to be a complex network by distinct signaling pathways.Defect of DDR pathways will sen-sitize cancer cells to chemo-radiotherapeutics.Targeting DDR pathways in DDR abnormal changed cancer individuals may increase the specificity and reduce toxicity.It will enforce the efficiency of genotoxic reagent and decrease the dose in cancer therapy.The successful example is using single strand break repair inhibitor(PARPi)for BRCA1/2 mutated cancer cells.More DDR inhibitors are exploring in preclinical and clinical trials,including inhibitors of ATR,CHK1,WEE1 and DNA-PK.A number of DDR-related genes were discovered owning driver gene mutations,while not all mu-tants are influencing the function of proteins.The abnormal changes of other modifications may also affect the DDR sig-naling function.Based on aberrant epigenetic induced DDR dysregulation has been developed"synthetic lethality"strategy and the efficiency has been verified by experiment.
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