Unleashing viral mimicry: A combinatorial strategy to enhance the efficacy of PARP7 inhibitors DOI Creative Commons

Patrick Manetsch,

Michael O. Hottiger

BioEssays, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 6, 2024

Abstract Cancer cells exploit mechanisms to evade immune detection triggered by aberrant self‐nucleic acids (NA). PARP7, a key player in this evasion strategy, has emerged as potential target for cancer therapy. PARP7 inhibitors reactivate NA sensing, resulting type I interferon (IFN) signaling, programmed cell death, anti‐tumor immunity, and tumor regression. with elevated IFN‐stimulated gene (ISG) scores, representing viral mimicry‐primed state, are particularly sensitive inhibition. This review focuses on the endogenous sources of self‐NA We describe strategies increase cytoplamic levels, including targeting epigenetic control, DNA damage response, mitochondrial function. also discuss RNA processing pathways, such splicing editing, enhance immunostimulatory existing NA. Combining elevating may improve immunotherapy, especially tumors high ISG scores.

Язык: Английский

PARP7 as a new target for activating anti-tumor immunity in cancer DOI Creative Commons

K. Popova,

Johannes Benedum, Magdalena Engl

и другие.

EMBO Molecular Medicine, Год журнала: 2025, Номер unknown

Опубликована: Март 24, 2025

Abstract ADP-ribosyl transferases (ARTs) are a family of enzymes which catalyze the addition chain (PARylation) or single moiety (MARylation) ADP-ribose to their substrates. PARP7 is mono-ADP-ribosyl transferase (mono-ART) has recently gained attention due its emerging role as negative regulator type I interferon (IFN-I) and nuclear receptor signaling, aberrant expression in cancer, contributing disease progression immune evasion. PARP7-mediated ADP-ribosylation can differentially affect protein stability. On one hand, transcription factor FRA1 protects it from proteosomal degradation thereby supports function negatively regulating IRF1 apoptosis signaling genes. other aryl hydrocarbon (AHR) estrogen (ER) marks them for degradation. also ADP-ribosylates ligand-bound androgen (AR), recognized by DTX3L-PARP9 that modulate AR transcriptional activity. In this review, we discuss enzymatic properties, biological functions known substrates, various cancers, targeting specific inhibitors.

Язык: Английский

Процитировано

0
Targeting selective inhibitors of PARPs in drug discovery and development DOI

Maolin Duan,

Jing Gao, Jiajin Li

и другие.

Medicinal Chemistry Research, Год журнала: 2024, Номер 33(10), С. 1734 - 1756

Опубликована: Июль 28, 2024

Язык: Английский

Процитировано

2
Unleashing viral mimicry: A combinatorial strategy to enhance the efficacy of PARP7 inhibitors DOI Creative Commons

Patrick Manetsch,

Michael O. Hottiger

BioEssays, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 6, 2024

Abstract Cancer cells exploit mechanisms to evade immune detection triggered by aberrant self‐nucleic acids (NA). PARP7, a key player in this evasion strategy, has emerged as potential target for cancer therapy. PARP7 inhibitors reactivate NA sensing, resulting type I interferon (IFN) signaling, programmed cell death, anti‐tumor immunity, and tumor regression. with elevated IFN‐stimulated gene (ISG) scores, representing viral mimicry‐primed state, are particularly sensitive inhibition. This review focuses on the endogenous sources of self‐NA We describe strategies increase cytoplamic levels, including targeting epigenetic control, DNA damage response, mitochondrial function. also discuss RNA processing pathways, such splicing editing, enhance immunostimulatory existing NA. Combining elevating may improve immunotherapy, especially tumors high ISG scores.

Язык: Английский

Процитировано

0