Integrated Manifestations of Cellular Stress as a Trigger of Tumor Progression - Cytology and Genetics

Abstract— In recent decades, the efforts of specialists from different fields of medicine were aimed at determining the role of stress in the development of cancer and subsequent tumor progression due to the invasive–migratory spread of malignantly transformed cells and formation of metastasis. Only subjective statements about the existence of an association between the development of a malignant process and the effect of factors that can cause malignant transformation of the cells are not enough. To date, the results of the studies obtained in the experiments in vitro and in vivo or confirmed by multiple clinical observations ex vivo are recognized as evidence-based. The literature review addresses the issues of the manifestations of stress at the cellular level, which is considered as a trigger of tumor progression. It was demonstrated that the cellular stress covers a wide range of intracellular structural and functional changes and molecular rearrangements that occur in the cells in response to environmental stress factors, including mechanical damage, extreme temperatures, effects of trauma, hypoxia, oxidative stress, as well as some viral infections. The mechanisms, by which intracellular disorders contribute to malignant growth and progression of neoplasms of different histogenesis, were characterized. Particularly, these include DNA damage, formation of unfolded protein, mitochondrial signaling stress, stress of endoplasmic reticulum, proliferation or elimination of damaged cells. It was demonstrated that the cells can respond to stress in different ways, ranging from the activation of survival pathways to initiation of cell death. Thus, it is necessary to consider structural and functional and molecular biological changes at the cellular and subcellular levels (occurring as a result of cellular stress), on the one hand, as possible targets when developing the methods of targeted chemotherapy and, on the other hand, when planning the means of preventing the occurrence of malignant neoplasms.