Activators and Inhibitors of NRF2: A Review of Their Potential for Clinical Development

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Activators and Inhibitors of NRF2: A Review of Their Potential for Clinical Development hindawi.com/journals/omcl/2...

Lots of interesting reading in here. I will just share the cautionary part:

4. Pharmacologic Inhibitors of NRF2

The implication of NRF2 in cancer is still controversial. Several studies described that NRF2 knockout mice are more susceptible to chemically induced carcinogenesis, pointing NRF2 as a potential tumor suppressor that limits carcinogenesis [136, 137]. On the other hand, NRF2 is overexpressed in many types of tumors, and it has been related to poor disease prognosis because it confers a survival and growth advantage to cancer cells, along with resistance to chemo- and radiotherapy [138–140]. Altogether, these results suggest a protective role of NRF2 in the first steps of cancer, but in advanced stages, NRF2 overexpression helps cancer cells to adapt to the tumorigenic demands. Cancer cells are “addicted” to NRF2 and resist treatment with chemotherapy or radiotherapy [141, 142]. Therefore, it is reasonable to assume that NRF2 inhibitors should sensitize tumor cells to anticancer therapies. In all cases, the mechanism of inhibition is either unknown or not specific, and therefore, NRF2 inhibitors are still far from being translated from bench to bedside.