Poly(ADP-ribose) polymerase 1 (PARP1) is a key mediator of various forms
of DNA damage repair and plays an important role in the progression of
several cancer types. The enzyme is activated by binding to DNA
single-strand and double-strand breaks. Its contribution to chromatin
remodeling makes PARP1 crucial for gene expression regulation.
Inhibition of its activity with small molecules leads to the synthetic
lethal effect by impeding DNA repair in the treatment of cancer cells.
At first, PARP1 inhibitors (PARPis) were developed to target breast
cancer mutated cancer cells. Currently, PARPis are being studied to be
used in a broader variety of patients either as single agents or in
combination with chemotherapy, antiangiogenic agents, ionizing
radiation, and immune checkpoint inhibitors. Ongoing clinical trials on
olaparib, rucaparib, niraparib, veliparib, and the recent talazoparib
show the advantage of these agents in overcoming PARPi resistance and
underline their efficacy in targeted treatment of several hematologic
malignancies. In this review, focusing on the crucial role of PARP1 in
physiological and pathological effects in myelodysplastic syndrome and
acute myeloid leukemia, we give an outline of the enzyme's mechanisms of
action and its role in the pathophysiology and prognosis of
myelodysplastic syndrome/acute myeloid leukemia and we analyze the
available data on the use of PARPis, highlighting their promising
advances in clinical application