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Drug resistance remains one of the leading bottlenecks contributing to unsatisfactory therapeutic outcomes and eventual treatment failure during clinical cancer chemotherapy, and abundant preclinical evidence has confirmed that abnormally elevated NNMT expression is closely correlated with acquired drug resistance across various solid and hematologic malignancies

For instance, experimental evidence suggestive for SSc having a paraneoplastic origin has been provided in association with mutated RNA pol III antigen [38]

Meanwhile, mTORC1/S6K1 can also phosphorylate IRS-1 serine, thus block its activation 80 (Fig

On one hand, it activates the Nrf2 pathway via VDR, inducing the expression of antioxidant enzymes such as superoxide dismutase (SOD), GPX, and CAT to increase ROS scavenging, while simultaneously downregulating iNOS and NADPH oxidase to limit ROS production ( 2+ CAMKK2AMPK signaling pathway ( Clinical and preclinical studies support these antioxidant effects