Therapeutic Application of PARP Inhibitors in Neuro-Oncology

Jianfang Ning; Hiroaki Wakimoto

doi:10.1016/j.trecan.2019.12.004

Therapeutic Application of PARP Inhibitors in Neuro-Oncology

Jianfang Ning, Hiroaki Wakimoto

Research output: Contribution to journal › Review article › peer-review

8 Scopus citations

Abstract

In response to a variety of cellular stresses, poly(ADP-ribose) polymerase 1 (PARP1) has vital roles in orchestrating DNA damage repair and preserving genomic integrity. Clinical activity of PARP inhibitors (PARPis) in BRCA1/2 mutant cancers validated the concept of synthetic lethality between PARP inhibition and deleterious BRCA1/2 mutations, leading to clinical approval of several PARPis. Preclinical and clinical studies aiming to broaden the therapeutic application of PARPis identified sensitivity biomarkers and rationale combination strategies that can target BRCA wild-type and homologous recombination (HR) DNA repair-proficient cancers, including central nervous system (CNS) malignancies. In this review, we summarize recent progress in PARPi therapy in brain tumors, and discuss current opportunities for, and challenges to, the use of PARPis in neuro-oncology.

Original language	English (US)
Pages (from-to)	147-159
Number of pages	13
Journal	Trends in Cancer
Volume	6
Issue number	2
DOIs	https://doi.org/10.1016/j.trecan.2019.12.004
State	Published - Feb 2020

Bibliographical note

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

DNA damage response
Poly(ADP-ribose) polymerase inhibitor
combination therapy
homologous recombination repair
neuro-oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.trecan.2019.12.004

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title = "Therapeutic Application of PARP Inhibitors in Neuro-Oncology",

abstract = "In response to a variety of cellular stresses, poly(ADP-ribose) polymerase 1 (PARP1) has vital roles in orchestrating DNA damage repair and preserving genomic integrity. Clinical activity of PARP inhibitors (PARPis) in BRCA1/2 mutant cancers validated the concept of synthetic lethality between PARP inhibition and deleterious BRCA1/2 mutations, leading to clinical approval of several PARPis. Preclinical and clinical studies aiming to broaden the therapeutic application of PARPis identified sensitivity biomarkers and rationale combination strategies that can target BRCA wild-type and homologous recombination (HR) DNA repair-proficient cancers, including central nervous system (CNS) malignancies. In this review, we summarize recent progress in PARPi therapy in brain tumors, and discuss current opportunities for, and challenges to, the use of PARPis in neuro-oncology.",

keywords = "DNA damage response, Poly(ADP-ribose) polymerase inhibitor, combination therapy, homologous recombination repair, neuro-oncology",

author = "Jianfang Ning and Hiroaki Wakimoto",

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AU - Wakimoto, Hiroaki

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AB - In response to a variety of cellular stresses, poly(ADP-ribose) polymerase 1 (PARP1) has vital roles in orchestrating DNA damage repair and preserving genomic integrity. Clinical activity of PARP inhibitors (PARPis) in BRCA1/2 mutant cancers validated the concept of synthetic lethality between PARP inhibition and deleterious BRCA1/2 mutations, leading to clinical approval of several PARPis. Preclinical and clinical studies aiming to broaden the therapeutic application of PARPis identified sensitivity biomarkers and rationale combination strategies that can target BRCA wild-type and homologous recombination (HR) DNA repair-proficient cancers, including central nervous system (CNS) malignancies. In this review, we summarize recent progress in PARPi therapy in brain tumors, and discuss current opportunities for, and challenges to, the use of PARPis in neuro-oncology.

KW - DNA damage response

KW - Poly(ADP-ribose) polymerase inhibitor

KW - combination therapy

KW - homologous recombination repair

KW - neuro-oncology

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Therapeutic Application of PARP Inhibitors in Neuro-Oncology

Abstract

Bibliographical note

Keywords

UN SDGs

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