THE ROLE OF THE RENIN-ANGIOTENSIN SYSTEM IN MALIGNANCY DEVELOPMENT IN THE LIGHT OF THE CONCEPT OF D. HANAHAN AND R. WEINBERG “THE HALLMARKS OF CANCER”
Abstract
Due to the emergence of a large number of studies on the role of the renin-angiotensin system (RAS) in the mechanisms of the development of malignant tumors, it seems very relevant to structure these data within the framework of the integral concept of D. Hanahan and R. Weinberg “The Hallmarks of Cancer”. It turns out that the renin-angiotensin system plays a significant role in the genesis of almost all “The Hallmarks of Cancer” mainly through the activation of the ACE (angiotensin-converting enzyme) / Ang II (angiotensin II)/ATR1 (angiotensin II receptors type 1) axis and renin/prorenin receptors (PRRs), which increase tumor-associated inflammation. Activation of transcription factors NFκB and STAT-3 plays a primary role here. In addition, due to the presence of angiotensin II receptors on lymphocytes and macrophages, RAS may be directly involved in modulating of the immune response. Localization of intracellular RAS receptors on mitochondria allows this system to participate in changing the metabolism of tumor cells. The relationship of RAS with the mechanisms of cellular aging has also been revealed. It has been shown that RAS interacts with the microbiome. At the same time, the opinion about the unequivocal oncoprotection of the ACE 2 (angiotensin-converting enzyme 2) / Ang (1-7) (angiotensin 1-7) / MasR (Mas receptors) axis seems to be not fully justified. The complexity of the structure of the RAS, its relationship with the kallikrein-kinin system and the complement system, the dynamic nature of the tumor process, and the extremely high phenotypic plasticity of tumor cells can lead to ambiguous effects on this system, which is confirmed by contradictory clinical data. In the experiment, a number of very encouraging results have already been obtained from the use of angiotensin II receptor blockers and ACE inhibitors in hepatocellular carcinoma, myeloid leukemia, prostate cancer, lung cancer, ovarian cancer, glioblastoma, and other tumors. Further research of the role of RAS in the mechanisms of tumor development opens up new opportunities for the use of drugs that affect this system in oncological practice.
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