ReviewPARP-inhibitor-induced synthetic lethality for acute myeloid leukemia treatment

•PARPi's may be used for synthetic lethal targeting of cancer genomes.•PARPi-induced synthetic lethality targets aberrant transcription programs.•PARPi's may be useful as monotherapy in AML.•PARPi's may be useful in combination with other agents in AML.

Genomic instability is one of the most common and critical characteristics of cancer cells. The combined effect of replication stress and DNA damage repair defects associated with various oncogenic events drives genomic instability and disease progression. However, these DNA repair defects found in cancer cells can also provide unique therapeutic opportunities and form the basis of synthetic lethal targeting of solid tumors carrying BRCA mutations. Although the idea of utilizing synthetic lethality as a therapy strategy has been gaining momentum in various solid tumors, its application in leukemia still largely lags behind. In this article, we review recent advances in understanding the roles of the DNA damage response in acute myeloid leukemia and examine the potential therapeutic avenues of using poly (ADP-ribose) polymerase (PARP) inhibitors in AML treatment.