Targeting ataxia-telangiectasia mutated deficient malignancies with poly ADP ribose polymerase inhibitors

Small molecule inhibitors of poly ADP ribose polymerase (PARP) have shown considerable promise as therapeutic agents in human malignancies with disruption of the breast and ovarian cancer susceptibility genes BRCA1 or BRCA2. Evidence is also accumulating that disruption of other genes involved in the detection and/or repair of DNA damage, in particular DNA double strand breaks (DSBs), may also have a synthetic lethal relationship with PARP. One of these is the DNA damage activated protein kinase, ataxia-telangiectasia mutated (ATM). Several studies have shown that ATM deficiency is common in a broad range of hematological and solid malignancies. Here, we discuss the potential for using PARP inhibitors in human cancers with mutation or disruption of ATM.