Targeting DNA repair pathways in AML

Abstract

Cancer cells often have DNA repair pathway deficiencies, which render cancer more sensitive to treatment but can also cause resistance if the DNA repair pathway is restored. By using DNA repair pathway inhibitors, cancers can be resensitized to conventional therapies, such as radiation and chemotherapy. There are 6 major DNA repair pathways, and each pathway has druggable targets and biomarkers to identify pathway activity. DNA repair inhibitors, such as poly-ADP-ribose polymerase (PARP) inhibitors, may be useful in a small subset of acute myeloid leukemia (AML) patients, especially those who have complex karyotypes or those with secondary AML. Biomarkers in the Fanconi anemia repair pathway may provide a predictor to identify this subset of patients who are sensitive to this new class of drugs.