Alterations of DNA damage response pathway: Biomarker and therapeutic strategy for cancer immunotherapy.
10.1016/j.apsb.2021.01.003
- Author:
Minlin JIANG
1
;
Keyi JIA
1
;
Lei WANG
1
;
Wei LI
1
;
Bin CHEN
1
;
Yu LIU
1
;
Hao WANG
1
;
Sha ZHAO
1
;
Yayi HE
1
;
Caicun ZHOU
1
Author Information
1. Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai 200433, China.
- Publication Type:Review
- Keywords:
ATM, ataxia-telangiectasia mutated;
ATR, ataxia telangiectasia and Rad3 related;
BAP1, BRCA1-associated protein 1;
BER, base excision repair;
BRAF, v-RAF murine sarcoma viral oncogene homologue B;
BRCA, breast cancer susceptibility gene;
CHEK, cell-cycle checkpoint kinase;
CHK1, checkpoint kinase 1;
DAMP, damage-associated molecular patterns;
DDR, DNA damage response;
DNA damage response;
DNA repair;
DR, direct repair;
DSBs, double-strand breaks;
FDA, United State Food and Drug Administration;
GSK3β, glycogen synthase kinase 3β;
Genomic instability;
HMGB1, high mobility group box-1;
HRR, homologous recombination repair;
ICI, immune checkpoint inhibitor;
IFNγ, interferon gamma;
IHC, immunohistochemistry;
IRF1, interferon regulatory factor 1;
Immunotherapy;
JAK, Janus kinase;
MAD1, mitotic arrest deficient-like 1;
MGMT, O6-methylguanine methyltransferase;
MLH1, MutL homolog 1;
MMR, mismatch repair;
MNT, MAX network transcriptional repressor;
MSH2/6, MutS protein homologue-2/6;
MSI, microsatellite instability;
MUTYH, MutY homolog;
MyD88, myeloid differentiation factor 88;
NEK1, NIMA-related kinase 1;
NER, nucleotide excision repair;
NGS, next generation sequencing;
NHEJ, nonhomologous end-joining;
NIMA, never-in-mitosis A;
NSCLC, non-small cell lung cancer;
ORR, objective response rate;
OS, overall survival;
PALB2, partner and localizer of BRCA2;
PARP, poly-ADP ribose polymerase;
PCR, polymerase chain reaction;
PD-1;
PD-1, programmed death 1;
PD-L1;
PD-L1, programmed death ligand 1;
PFS, progression-free survival;
RAD51C, RAD51 homolog C;
RB1, retinoblastoma 1;
RPA, replication protein A;
RSR, replication stress response;
SCNAs, somatic copy number alterations;
STAT, signal transducer and activator of transcription;
STING, stimulator of interferon genes;
TBK1, TANK-binding kinase 1;
TILs, tumor-infiltrating lymphocytes;
TLR4, Toll-like receptor 4;
TMB, tumor mutational burden;
TME, tumor microenvironment;
TP53, tumor protein P53;
TRIF, Toll-interleukin 1 receptor domain-containing adaptor inducing INF-β;
Tumor microenvironment;
XRCC4, X-ray repair cross complementing protein 4;
cGAS, cyclic GMP–AMP synthase;
cGAS–STING;
ssDNA, single-stranded DNA
- From:
Acta Pharmaceutica Sinica B
2021;11(10):2983-2994
- CountryChina
- Language:English
-
Abstract:
Genomic instability remains an enabling feature of cancer and promotes malignant transformation. Alterations of DNA damage response (DDR) pathways allow genomic instability, generate neoantigens, upregulate the expression of programmed death ligand 1 (PD-L1) and interact with signaling such as cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling. Here, we review the basic knowledge of DDR pathways, mechanisms of genomic instability induced by DDR alterations, impacts of DDR alterations on immune system, and the potential applications of DDR alterations as biomarkers and therapeutic targets in cancer immunotherapy.
