抑制NRF2，延缓耐药，延长生命

一、nrf2表达高，预后差

1、《The prognostic value of NRF2 in breast cancer patients: a systematic review with meta-analysis》 这篇论文讲了nrf2表达与乳腺癌预后的一项荟萃分析。

“与低NRF2表达的患者相比，NRF2过表达的患者OS更差，风险比为1.82(95% CI 1.32-2.50；p值<  0.0001)，和较差的DFS，风险比为1.79(95% CI 1.07-3.01；p值= 0.03)。” “For the meta-analysis, seven studies were included and NRF2 expression was correlated with OS and DFS. It was observed that compared to patients with low NRF2 expression, patients with NRF2 overexpression had poorer OS with a hazard ratio of 1.82 (95% CI 1.32-2.50; p value < 0.0001), and poorer DFS, with a hazard ratio of 1.79 (95% CI 1.07-3.01; p value = 0.03).” （《The prognostic value of NRF2 in breast cancer patients: a systematic review with meta-analysis》）
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2、《Prognostic and clinicopathological significance of NRF2 expression in non-small cell lung cancer: A meta-analysis》 这篇论文讲了nrf2表达与非小细胞肺癌预后的一项荟萃分析。

4 t% f. a1 H8 C: e0 b“NRF2的高表达水平预示着较差的总生存率(HR = 1.86，95% CI 1.44-2.41，P < 0.001)和较差的无进展生存率(PFS) (HR = 2.27，95% CI 1.26-4.09，P = 0.006)。与低水平NRF2表达的患者相比，当给予化疗或EGFR-TKI时，高水平NRF2表达的患者与更差的OS和PFS相关。” “High expression level of NRF2 is predictive for poor overall survival rate (HR = 1.86, 95% CI 1.44-2.41, P < 0.001) and poor progression-free survival (PFS) (HR = 2.27, 95% CI 1.26-4.09, P = 0.006). Compared to patients with a low level of NRF2 expression, patients with high NRF2 expression levels were associated with worse OS and PFS when given the chemotherapy or EGFR-TKI. Together, our meta-analysis results suggest that NRF2 can act as a potential indicator of NSCLC tumour aggressiveness and help the prognosis and design of a better treatment strategy for NSCLC patients.”

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8 f% {7 @4 z& A, K目前没有专门的NRF2靶向药上市，有一些替代药物
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, o9 Q% R1 g* z3 z" s" K“we screened ~4000 clinical compounds and determined clobetasol propionate (CP) as the most potent NRF2 inhibitor.” （《A clinical drug library screen identifies clobetasol propionate as an NRF2 inhibitor with potential therapeutic efficacy in KEAP1 mutant lung cancer》）

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“These findings suggest that luteolin treatment significantly attenuated the hallmarks of breast cancer stemness by downregulating Nrf2-mediated expressions. ” （《Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway》）
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7 ?5 o2 Y) c+ G3、白杨素
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“Mechanistically, chrysin significantly reduced Nrf2 expression at both the mRNA and protein levels through down-regulating PI3K-Akt and ERK pathway.” （《Chrysin enhances sensitivity of BEL-7402/ADM cells to doxorubicin by suppressing PI3K/Akt/Nrf2 and ERK/Nrf2 pathway》）
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: Y2 w2 ?) A0 |4、布洛芬
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“our findings reveal that ibuprofen could induce ferroptosis of glioblastoma cells via downregulation of Nrf2 signaling pathway and is a potential drug for glioma treatment.” （《Ibuprofen induces ferroptosis of glioblastoma cells via downregulation of nuclear factor erythroid 2-related factor 2 signaling pathway》）
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