NON-CYCLOOXYGENASE SIGNALING PATHWAYS AS A MECHANISM OF THERAPEUTIC ACTIVITY OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS IN ANTICANCER THERAPY
DOI:
https://doi.org/10.32689/2663-0672-2023-1-3Keywords:
non-steroidal anti-inflammatory drugs, extra-cyclooxygenase effects, PI3K/Akt/mTOR, PI3K/PTEN/Akt, NAG-1, Wnt/β-cateninAbstract
Introduction. Inflammation is closely related to the tumor process and plays a key role in the formation and progression of neoplasms. Tumor cells are phenotypically similar to inflammatory cells because they express cytokines, chemokines and their receptors. In recent decades, nonsteroidal anti-inflammatory drugs (NSAIDs) have been found to reduce mortality from certain types of cancer, such as colon, ovarian, prostate, skin, esophagus, pancreas, breast, bladder, head and neck, and also with hepatocellular carcinoma. Elucidation of the role of inflammatory mediators in tumorigenesis, angiogenesis, and metastasis in recent years, as well as data from epidemiological studies of the effectiveness of NSAIDs in the prevention of cancer diseases, create prerequisites for active research into the molecular mechanisms of the anticancer activity of drugs of this group. The aim of the study was to summarize the current information on cyclooxygenase-independent signaling pathways that are affected by NSAIDs as possible targets in the treatment of cancer patients. Materials and methods. Publications were selected based on PubMed, Clinical Key Elsevier, Cochrane Library, etc. databases, which covered information on the use of NSAIDs in the treatment of oncological diseases. Research results and their discussion. Activation of mitogen-activated kinases (MAPK), the NF-κB pathway, the PI3K/Akt/ mTOR pathway, and the Wnt/β-catenin pathway affects the key processes of tumor growth, metastasis, and apoptosis in cancer cells. Inhibition of these signaling pathways with NSAIDs can inhibit cell growth, promote apoptosis, and reduce invasiveness of cancer cells. In addition, the identification of genes regulated by NSAIDs opens up opportunities for further understanding of the molecular mechanisms of the antitumor activity of these drugs. Research in the field of signaling pathways shows the potential effectiveness of NSAIDs in the treatment of various types of cancer and the expansion of their use in anticancer therapy. Conclusions. Studies of non-cyclooxygenase effects of NSAIDs serve as a basis for conducting clinical studies of new approaches to the regulation of tumor signaling pathways and open perspectives for improving cancer treatment strategies.
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