Histone-dependent PARP-1 inhibitors: A novel therapeutic modality for the treatment of prostate and renal cancers

Urol Oncol. 2021 Jun;39(6):312-315. doi: 10.1016/j.urolonc.2020.04.004. Epub 2020 May 8.


Clinical interest in poly(ADP-ribose) polymerase 1 (PARP-1) has increased over the past decade with the recognition of its roles in transcription regulation, DNA repair, epigenetic bookmarking, and chromatin restructuring. A number of PARP-1 inhibitors demonstrating clinical efficacy against tumors of various origins have emerged in recent years. These inhibitors have been essentially designed as nicotinamide adenine dinucleotide (NAD+) mimetics. However, because NAD+ is utilized by many enzymes other than PARP-1, NAD+ competitors tend to produce certain off-target effects. To overcome the limitation of NAD-like PARP-1 inhibitors, we have developed a new class of PARP-1 inhibitors that specifically targets the histone-dependent route of PARP-1 activation, a mechanism of activation that is unique to PARP-1. Novel histone-dependent inhibitors are highly specific for PARP-1 and demonstrate promising in vitro and in vivo efficacy against prostate and renal tumors. Our findings suggest that novel PARP-1 inhibitors have strong therapeutic potential for the treatment of urological tumors.

Keywords: Histone-dependent PARP-1 regulation; NAD(+); PARP-1 inhibitors; Prostate cancer; Renal cell carcinoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Histones
  • Humans
  • Kidney Neoplasms / drug therapy*
  • Male
  • Poly (ADP-Ribose) Polymerase-1 / antagonists & inhibitors*
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use*
  • Prostatic Neoplasms / drug therapy*


  • Histones
  • Poly(ADP-ribose) Polymerase Inhibitors
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1