PARP Inhibitors in Cancers

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: closed (20 December 2023) | Viewed by 4915

Special Issue Editors


E-Mail Website1 Website2
Guest Editor
Department of Immunology and Cell Biology, Institute of Parasitology and Biomedicine “López-Neyra”, IPBLN, CSIC, CIBERONC, 18016 Granada, Spain
Interests: PARP; hypoxia; tumor microenvironment; PARP inhibitor; mitochondrial diseases

E-Mail Website
Guest Editor
1. Cancer Research Program, Hospital del Mar Medical Research Institute, 08003 Barcelona, Spain
2. Laboratory of Immunology, Department of Pathology, Hospital del Mar, 08003 Barcelona, Spain
Interests: PARP; DNA damage; tumor cell; immune response
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Special Issue Information

Dear Colleagues,

The deeper understanding of DNA repair mechanisms and their potential value as therapeutic targets in oncology heralded the clinical development of a wide range of chemical inhibitors, targeting several enzymes working on signal DNA damage, modulating chromatin architecture or inhibiting specific DNA repair pathways, whose activity was certainly uncontrolled in cancer cells. Poly (ADP-ribose) polymerase (PARP) inhibitors represent a novel and effective class of anti-cancer therapy, highlighting the importance of the synthetic lethality concept in cancer progression, focusing on cells lacking homologous recombination DNA repair. Biochemically, PARP inhibition leads to the accumulation of DNA damage by impairing single-strand break sites, trapping DNA-dependent PARP at these SSBR sites and leading to the inhibition of DNA replication.

However, the mechanism is much more complex and the biology of PARP enzymes inhibition is still far from fully understood. This misinformation has triggered a multitude of projects and groups that have opened new lines of research in cancer, neurodegenerative diseases, metabolic or cardiac diseases, enriching knowledge about the therapeutic potential of PARP inhibitors.

This Special Issue welcomes both original research manuscripts as well as reviews focusing on the current state of PARP inhibitors in cancer therapy.

Dr. Jose Manuel Rodriguez-Vargas
Dr. José Yélamos
Guest Editors

Manuscript Submission Information

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Keywords

  • PARP inhibitors
  • clinical relevance
  • cancer progression
  • DNA repair mechanisms
  • cancer cells

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Published Papers (1 paper)

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Review

24 pages, 1511 KiB  
Review
Pharmacologic Induction of BRCAness in BRCA-Proficient Cancers: Expanding PARP Inhibitor Use
by Rachel Abbotts, Anna J. Dellomo and Feyruz V. Rassool
Cancers 2022, 14(11), 2640; https://doi.org/10.3390/cancers14112640 - 26 May 2022
Cited by 20 | Viewed by 4378
Abstract
The poly(ADP-ribose) polymerase (PARP) family of proteins has been implicated in numerous cellular processes, including DNA repair, translation, transcription, telomere maintenance, and chromatin remodeling. Best characterized is PARP1, which plays a central role in the repair of single strand DNA damage, thus prompting [...] Read more.
The poly(ADP-ribose) polymerase (PARP) family of proteins has been implicated in numerous cellular processes, including DNA repair, translation, transcription, telomere maintenance, and chromatin remodeling. Best characterized is PARP1, which plays a central role in the repair of single strand DNA damage, thus prompting the development of small molecule PARP inhibitors (PARPi) with the intent of potentiating the genotoxic effects of DNA damaging agents such as chemo- and radiotherapy. However, preclinical studies rapidly uncovered tumor-specific cytotoxicity of PARPi in a subset of cancers carrying mutations in the BReast CAncer 1 and 2 genes (BRCA1/2), which are defective in the homologous recombination (HR) DNA repair pathway, and several PARPi are now FDA-approved for single agent treatment in BRCA-mutated tumors. This phenomenon, termed synthetic lethality, has now been demonstrated in tumors harboring a number of repair gene mutations that produce a BRCA-like impairment of HR (also known as a ‘BRCAness’ phenotype). However, BRCA mutations or BRCAness is present in only a small subset of cancers, limiting PARPi therapeutic utility. Fortunately, it is now increasingly recognized that many small molecule agents, targeting a variety of molecular pathways, can induce therapeutic BRCAness as a downstream effect of activity. This review will discuss the potential for targeting a broad range of molecular pathways to therapeutically induce BRCAness and PARPi synthetic lethality. Full article
(This article belongs to the Special Issue PARP Inhibitors in Cancers)
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