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The Role of the Integrated Response of Tumor Cells to Stress, Autophagy, and Chaperones in the Origin of Recurrent Resistant Tumors

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Abstract

Chemotherapy and radiotherapy are colossal stress factors for tumor cells. In response to therapy, the entire evolutionarily fixed response of cells to stress is activated. This happens at all levels of cell organization, namely, at the protein level and the DNA level. This response includes the cell proteostasis system, DNA-repair systems, tumor-suppressor genes, and many other cell systems. We will consider the role of the main systems of proteostasis in these processes, namely, macroautophagy and chaperones, which are parts of the integrated cell response to stress. As a result of the cell’s response to stress, the tumor cell becomes even less differentiated, activating the genes and intracellular systems necessary for survival. Cells that have responded to stress in this way have a more aggressive phenotype that is significantly more resistant to therapy. Under the influence of stress, the cell evolutionarily simplifies, which gives it additional chances for survival. Autophagy, on one hand, contributes to a decrease in tumor-cell differentiation and its plasticity, and, on the other hand, it maintains a certain stability, being responsible for the integrity of the genome and freeing the cell from damaged organelles and defective proteins. Both autophagy and chaperones contribute to the acquisition of multidrug resistance by the tumor, which further complicates therapy. Understanding these processes, taking into account the multistage nature of carcinogenesis, makes it possible to develop new therapeutic approaches.

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This work was carried out with the financial support of the Russian Science Foundation, project no. 22-25-20229 (https://rscf.ru/project/22-25-20229/).

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  1. Institute of Cytology, Russian Academy of Sciences, 194064, St. Petersburg, Russia

    S. G. Zubova & O. O. Gnedina

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Zubova, S.G., Gnedina, O.O. The Role of the Integrated Response of Tumor Cells to Stress, Autophagy, and Chaperones in the Origin of Recurrent Resistant Tumors. Cell Tiss. Biol. 17, 465–476 (2023). https://doi.org/10.1134/S1990519X23050139

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