Unleashing viral mimicry: A combinatorial strategy to enhance the efficacy of PARP7 inhibitors.

Autor: Manetsch P; Department of Molecular Mechanisms of Disease, University of Zurich, Zurich, Switzerland.; Molecular Life Science PhD Program of the Life Science Zurich Graduate School, University of Zurich, Zurich, Switzerland., Hottiger MO; Department of Molecular Mechanisms of Disease, University of Zurich, Zurich, Switzerland.
Jazyk: angličtina
Zdroj: BioEssays : news and reviews in molecular, cellular and developmental biology [Bioessays] 2024 Nov 06, pp. e2400087. Date of Electronic Publication: 2024 Nov 06.
DOI: 10.1002/bies.202400087
Abstrakt: Cancer cells exploit mechanisms to evade immune detection triggered by aberrant self-nucleic acids (NA). PARP7, a key player in this immune evasion strategy, has emerged as a potential target for cancer therapy. PARP7 inhibitors reactivate NA sensing, resulting in type I interferon (IFN) signaling, programmed cell death, anti-tumor immunity, and tumor regression. Cancer cells with elevated IFN-stimulated gene (ISG) scores, representing a viral mimicry-primed state, are particularly sensitive to PARP7 inhibition. This review focuses on the endogenous sources of NA in cancer and the potential to exploit elevated aberrant self-NA in cancer therapy. We describe strategies to increase cytoplamic NA levels, including targeting epigenetic control, DNA damage response, and mitochondrial function. We also discuss targeting RNA processing pathways, such as splicing and RNA editing, to enhance the immunostimulatory potential of existing NA. Combining PARP7 inhibitors with NA elevating strategies may improve cancer immunotherapy, especially for tumors with high ISG scores.
(© 2024 The Author(s). BioEssays published by Wiley Periodicals LLC.)
Databáze: MEDLINE
Externí odkaz: