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
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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 -