Aberrations in DNA repair pathways in cancer and therapeutic significances

Akira Motegi, Mitsuko Masutani, Ken ichi Yoshioka, Tadayoshi Bessho

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

Cancer cells show various types of mutations and aberrant expression in genes involved in DNA repair responses. These alterations induce genome instability and promote carcinogenesis steps and cancer progression processes. These defects in DNA repair have also been considered as suitable targets for cancer therapies. A most effective target so far clinically demonstrated is “homologous recombination repair defect”, such as BRCA1/2 mutations, shown to cause synthetic lethality with inhibitors of poly(ADP-ribose) polymerase (PARP), which in turn is involved in DNA repair as well as multiple physiological processes. Different approaches targeting genomic instability, including immune therapy targeting mismatch-repair deficiency, have also recently been demonstrated to be promising strategies. In these DNA repair targeting-strategies, common issues could be how to optimize treatment and suppress/conquer the development of drug resistance. In this article, we review the extending framework of DNA repair response pathways and the potential impact of exploiting those defects on cancer treatments, including chemotherapy, radiation therapy and immune therapy.

Original languageEnglish (US)
Pages (from-to)29-46
Number of pages18
JournalSeminars in Cancer Biology
Volume58
DOIs
StatePublished - Oct 2019

Fingerprint

DNA Repair
Genomic Instability
Neoplasms
Physiological Phenomena
Therapeutics
Recombinational DNA Repair
Mutation
Drug Resistance
Carcinogenesis
Radiotherapy
Gene Expression
Drug Therapy

Keywords

  • Homologous recombination repair
  • Mismatch repair
  • Nucleotide excision repair
  • PARP
  • Synthetic lethality

ASJC Scopus subject areas

  • Cancer Research

Cite this

Aberrations in DNA repair pathways in cancer and therapeutic significances. / Motegi, Akira; Masutani, Mitsuko; Yoshioka, Ken ichi; Bessho, Tadayoshi.

In: Seminars in Cancer Biology, Vol. 58, 10.2019, p. 29-46.

Research output: Contribution to journalReview article

Motegi, Akira ; Masutani, Mitsuko ; Yoshioka, Ken ichi ; Bessho, Tadayoshi. / Aberrations in DNA repair pathways in cancer and therapeutic significances. In: Seminars in Cancer Biology. 2019 ; Vol. 58. pp. 29-46.
@article{fdcc5e06fbc64050a8caddfcc310beb6,
title = "Aberrations in DNA repair pathways in cancer and therapeutic significances",
abstract = "Cancer cells show various types of mutations and aberrant expression in genes involved in DNA repair responses. These alterations induce genome instability and promote carcinogenesis steps and cancer progression processes. These defects in DNA repair have also been considered as suitable targets for cancer therapies. A most effective target so far clinically demonstrated is “homologous recombination repair defect”, such as BRCA1/2 mutations, shown to cause synthetic lethality with inhibitors of poly(ADP-ribose) polymerase (PARP), which in turn is involved in DNA repair as well as multiple physiological processes. Different approaches targeting genomic instability, including immune therapy targeting mismatch-repair deficiency, have also recently been demonstrated to be promising strategies. In these DNA repair targeting-strategies, common issues could be how to optimize treatment and suppress/conquer the development of drug resistance. In this article, we review the extending framework of DNA repair response pathways and the potential impact of exploiting those defects on cancer treatments, including chemotherapy, radiation therapy and immune therapy.",
keywords = "Homologous recombination repair, Mismatch repair, Nucleotide excision repair, PARP, Synthetic lethality",
author = "Akira Motegi and Mitsuko Masutani and Yoshioka, {Ken ichi} and Tadayoshi Bessho",
year = "2019",
month = "10",
doi = "10.1016/j.semcancer.2019.02.005",
language = "English (US)",
volume = "58",
pages = "29--46",
journal = "Seminars in Cancer Biology",
issn = "1044-579X",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Aberrations in DNA repair pathways in cancer and therapeutic significances

AU - Motegi, Akira

AU - Masutani, Mitsuko

AU - Yoshioka, Ken ichi

AU - Bessho, Tadayoshi

PY - 2019/10

Y1 - 2019/10

N2 - Cancer cells show various types of mutations and aberrant expression in genes involved in DNA repair responses. These alterations induce genome instability and promote carcinogenesis steps and cancer progression processes. These defects in DNA repair have also been considered as suitable targets for cancer therapies. A most effective target so far clinically demonstrated is “homologous recombination repair defect”, such as BRCA1/2 mutations, shown to cause synthetic lethality with inhibitors of poly(ADP-ribose) polymerase (PARP), which in turn is involved in DNA repair as well as multiple physiological processes. Different approaches targeting genomic instability, including immune therapy targeting mismatch-repair deficiency, have also recently been demonstrated to be promising strategies. In these DNA repair targeting-strategies, common issues could be how to optimize treatment and suppress/conquer the development of drug resistance. In this article, we review the extending framework of DNA repair response pathways and the potential impact of exploiting those defects on cancer treatments, including chemotherapy, radiation therapy and immune therapy.

AB - Cancer cells show various types of mutations and aberrant expression in genes involved in DNA repair responses. These alterations induce genome instability and promote carcinogenesis steps and cancer progression processes. These defects in DNA repair have also been considered as suitable targets for cancer therapies. A most effective target so far clinically demonstrated is “homologous recombination repair defect”, such as BRCA1/2 mutations, shown to cause synthetic lethality with inhibitors of poly(ADP-ribose) polymerase (PARP), which in turn is involved in DNA repair as well as multiple physiological processes. Different approaches targeting genomic instability, including immune therapy targeting mismatch-repair deficiency, have also recently been demonstrated to be promising strategies. In these DNA repair targeting-strategies, common issues could be how to optimize treatment and suppress/conquer the development of drug resistance. In this article, we review the extending framework of DNA repair response pathways and the potential impact of exploiting those defects on cancer treatments, including chemotherapy, radiation therapy and immune therapy.

KW - Homologous recombination repair

KW - Mismatch repair

KW - Nucleotide excision repair

KW - PARP

KW - Synthetic lethality

UR - http://www.scopus.com/inward/record.url?scp=85065753999&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065753999&partnerID=8YFLogxK

U2 - 10.1016/j.semcancer.2019.02.005

DO - 10.1016/j.semcancer.2019.02.005

M3 - Review article

C2 - 30922960

AN - SCOPUS:85065753999

VL - 58

SP - 29

EP - 46

JO - Seminars in Cancer Biology

JF - Seminars in Cancer Biology

SN - 1044-579X

ER -