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Therapy-Induced Tumor Cell Senescence: Mechanisms and Circumvention

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Abstract

Plasticity of tumor cells (multitude of molecular regulation pathways) allows them to evade cytocidal effects of chemo- and/or radiation therapy. Metabolic adaptation of the surviving cells is based on transcriptional reprogramming. Similarly to the process of natural cell aging, specific features of the survived tumor cells comprise the therapy-induced senescence phenotype. Tumor cells with this phenotype differ from the parental cells since they become less responsive to drugs and form aggressive progeny. Importance of the problem is explained by the general biological significance of transcriptional reprogramming as a mechanism of adaptation to stress, and by the emerging potential of its pharmacological targeting. In this review we analyze the mechanisms of regulation of the therapy-induced tumor cell senescence, as well as new drug combinations aimed to prevent this clinically unfavorable phenomenon.

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Abbreviations

BIRC5 :

gene encoding survivin protein

CDK:

cyclin-dependent protein kinase

EMT:

epithelial–mesenchymal transition

ROS:

reactive oxygen species

SASP:

senescence-associated secretory phenotype

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Funding

This work was financially supported by the Russian Science Foundation (grant no. 22-24-00212).

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Authors and Affiliations

  1. Institute of Gene Biology, Russian Academy of Sciences, 119334, Moscow, Russia

    Maria A. Zamkova, Nadezhda A. Persiyantseva & Victor V. Tatarskiy

  2. Blokhin National Medical Research Center of Oncology, 115478, Moscow, Russia

    Maria A. Zamkova, Nadezhda A. Persiyantseva & Alexander A. Shtil

  3. Institute of Cyber Intelligence Systems, National Research Nuclear University MEPHI, 115409, Moscow, Russia

    Alexander A. Shtil

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  1. Maria A. Zamkova
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  2. Nadezhda A. Persiyantseva
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  3. Victor V. Tatarskiy
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Zamkova, M. A. – writing and editing the text; Persiyantseva, N. A., Tatarskiy, V. V. – editing the text; Shtil, A. A. – conceptualization, writing, and final editing.

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Correspondence to Maria A. Zamkova.

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Zamkova, M.A., Persiyantseva, N.A., Tatarskiy, V.V. et al. Therapy-Induced Tumor Cell Senescence: Mechanisms and Circumvention. Biochemistry Moscow 88, 86–104 (2023). https://doi.org/10.1134/S000629792301008X

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  • DOI: https://doi.org/10.1134/S000629792301008X

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