PARP mediated DNA damage response, genomic stability and immune responses

Poly(ADP‐ribose) polymerase (PARP) enzymes, especially PARP1, play important roles in the DNA damage response and in the maintenance of genome stability, which makes PARPis a classic synthetic lethal therapy for BRCA‐deficient tumors. Conventional mechanisms suggest that PARPis exert their effects v...

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Veröffentlicht in:International journal of cancer 2022-06, Vol.150 (11), p.1745-1759
Hauptverfasser: Zong, Chunyan, Zhu, Tianyu, He, Jie, Huang, Rui, Jia, Renbing, Shen, Jianfeng
Format: Artikel
Sprache:eng
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Zusammenfassung:Poly(ADP‐ribose) polymerase (PARP) enzymes, especially PARP1, play important roles in the DNA damage response and in the maintenance of genome stability, which makes PARPis a classic synthetic lethal therapy for BRCA‐deficient tumors. Conventional mechanisms suggest that PARPis exert their effects via catalytic inhibition and PARP‐DNA trapping. Recently, PARP1 has been found to play a role in the immune modulation of tumors. The blockade of PARP1 is able to induce innate immunity through a series of molecular mechanisms, thus allowing the prediction of the feasibility of PARPis combined with immune agents in the treatment of tumors. PARPis combined with immunomodulators may have a stronger tumor suppressive effect on inhibiting tumor growth and blocking immune escape.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.33918