Poly (ADP-ribose) polymerase (PARP) inhibition in cancer: Potential impact in cancer stem cells and therapeutic implications

Abstract

Inhibitors of poly(ADP-ribose) polymerase (PARP) are used in mono- or combination therapies for several malignancies. They are also used as maintenance therapy for some cancers after initial treatment. While the focus of this therapeutic approach is on the effect of PARP inhibition on the bulk tumour cells, in this review, we discuss their effect on the cancer stem cells. We identify key mediators and pathways in cancer stem cells whose response to PARP inhibition is not necessarily the same as the rest of the tumour cells. Since the cancer stem cells are known drivers of growth of tumours and their resistance to therapy, the clinical outcome might be drastically different than what is expected, if the effect of PARP inhibition on the cancer stem cells is not taken into account.

Keywords: Cancer stem cells; Cancer therapy; Cell death; Differentiation; PARP; PARP-Inhibitors (PARPi).