REVIEW: Therapy-Induced Tumor Cell Senescence: Mechanisms and Circumvention

---

Maria A. Zamkova^1,2,a*, Nadezhda A. Persiyantseva^1,2, Victor V. Tatarskiy¹, and Alexander A. Shtil^2,3

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

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

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

^* To whom correspondence should be addressed.

Received October 7, 2022; Revised December 8, 2022; Accepted December 8, 2022

---

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.

---

KEY WORDS: transformed cells, cytotoxicity, intracellular signals, therapy-induced cell senescence, gene transcription, antitumor treatment

DOI: 10.1134/S000629792301008X

---