REVIEW: Role of Autophagy in the Mechanisms of Chemoresistance of Tumor Cells Induced by the Use of Anthracycline Antibiotics

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Nadezhda A. Persiyantseva¹, Ekaterina S. Ivanova^1,2 and Maria A. Zamkova^1,2,a*

¹Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, Russia

²Institute of Cyber Intelligence Systems, National Research Nuclear University MEPhI, 115409 Moscow, Russia

^* To whom correspondence should be addressed.

Received: April 8, 2025; Revised: June 4, 2025; Accepted: June 6, 2025

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Autophagy not only helps eliminate damaged, mutated, or genomically unstable cells, but also increases the chances of tumor cells overcoming the consequences of damage caused by chemotherapy. Autophagy induced by anthracyclines is cytoprotective in most tumor cell lines. Pharmacological or genetic blocking of autophagy in this case sensitizes tumor cells to therapy. Activation of cytoprotective autophagy can lead to chemoresistance, and with excessive enhancement, it can lead to energy depletion and trigger autophagic death. In some cases, cytotoxic autophagy develops under the action of anthracyclines, and its blocking increases cell survival. Activation of cytotoxic autophagy, on the contrary, triggers the process of “self-eating.” Modulation of autophagy in response to chemotherapeutic agents can be a double-edged sword for tumor cells, leading to both death and survival.

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KEY WORDS: tumor cells, autophagy, chemoresistance, chemotherapy, anthracycline antibiotics, doxorubicin, cell death, therapy-induced senescence

DOI: 10.1134/S0006297925601005

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