Korneenko, T.V.; Pestov, N.B.; Nevzorov, I.A.; Daks, A.A.; Trachuk, K.N.; Solopova, O.N.; Barlev, N.A. At the Crossroads of the cGAS-cGAMP-STING Pathway and the DNA Damage Response: Implications for Cancer Progression and Treatment. Pharmaceuticals2023, 16, 1675.
Korneenko, T.V.; Pestov, N.B.; Nevzorov, I.A.; Daks, A.A.; Trachuk, K.N.; Solopova, O.N.; Barlev, N.A. At the Crossroads of the cGAS-cGAMP-STING Pathway and the DNA Damage Response: Implications for Cancer Progression and Treatment. Pharmaceuticals 2023, 16, 1675.
Korneenko, T.V.; Pestov, N.B.; Nevzorov, I.A.; Daks, A.A.; Trachuk, K.N.; Solopova, O.N.; Barlev, N.A. At the Crossroads of the cGAS-cGAMP-STING Pathway and the DNA Damage Response: Implications for Cancer Progression and Treatment. Pharmaceuticals2023, 16, 1675.
Korneenko, T.V.; Pestov, N.B.; Nevzorov, I.A.; Daks, A.A.; Trachuk, K.N.; Solopova, O.N.; Barlev, N.A. At the Crossroads of the cGAS-cGAMP-STING Pathway and the DNA Damage Response: Implications for Cancer Progression and Treatment. Pharmaceuticals 2023, 16, 1675.
Abstract
The evolutionary conserved STING-cGAS pathway represents one of the most important cytosolic DNA sensing systems that is activated in response to viral invasion and/or damaged integrity of the nuclear envelope. The key outcome of this pathway is the production of IFN, which subsequently stimulates hundreds of genes. In oncology, the situation is a complex one since this pathway may serve either anti- or pro-oncogenic roles in a context-dependent fashion. The prevailing understanding is that when the innate immune response is activated by sensing cytosolic DNA, such as from ruptured micronuclei, it results in the production of interferon which attracts cytotoxic cells to destroy tumors. However, in tumor cells that have adjusted to significant chromosomal instability, particularly in relapsed, treatment-resistant cancers, the cGAS–STING pathway often supports cancer progression. In these cells, the pathway initiates a non-canonical nuclear factor κB transcriptional response, fostering the epithelial-to-mesenchymal transition (EMT). Here, we review this intricate pathway in conjunction with cancer progression and development of new treatment modalities.
Medicine and Pharmacology, Oncology and Oncogenics
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