NFE2L2 mutation

NRF2 directly binds to and transcriptionally activates CARM1, thereby enhancing ferroptosis resistance and promoting TNBC progression. These findings reveal a novel molecular mechanism underlying TNBC malignancy and suggest that targeting the NRF2-CARM1 axis, particularly in combination with ferroptosis inducers, may provide a potential strategy for TNBC treatment.

This large clinicogenomic study in an Asian population highlights unique mutational landscapes and survival associations, which may inform personalized treatment strategies.

The antidepressant effect of sustained vmPFC-DBS may rely on its antiinflammatory and antioxidative stress effects.

BET may promote ferroptosis-associated cell death and suppress breast cancer cell malignant phenotypes, potentially through modulation of the KEAP1/NRF2/xCT/GPX4 pathway. These findings suggest a possible therapeutic relevance of BET in breast cancer, although further in vivo and clinical validation is required.

This review focuses on targeting NRF2-driven metabolic dependencies as synthetic lethal vulnerabilities, spanning pathways such as glutaminolysis, redox imbalance, cystine metabolism, nucleotide biosynthesis and ER proteostasis. We also highlight emerging strategies, including allosteric KEAP1 activators, and discuss key challenges in translating these approaches into effective therapies.

Moreover, alterations in CCND1 and FGF family genes were associated with poor prognosis, highlighting their potential roles as prognostic biomarkers and therapeutic targets in ESCC. III.

These findings suggest that NFE2L2-mutated urothelial carcinomas frequently have concomitant squamous and myxoid features, aggressive behaviour and high PD-L1 expression. Recognition of the NFE2L2-mutated urothelial carcinomas may have diagnostic and prognostic utility, particularly with immunotherapy and possible targeted therapy against the NRF2 signalling pathway. Further investigation with larger cohorts is warranted to expand the data surrounding NFE2L2 mutations in urothelial carcinoma.

The retention of RB1 and the presence of the NFE2L2 mutation distinguish this entity from classic SCLC, supporting a reclassification as high-grade NSCLC. Recognition of this molecular subset is vital, as NFE2L2 mutations are theoretically linked to resistance to standard platinum-based regimens, potentially necessitating therapeutic strategies distinct from standard SCLC algorithms.

P1, N=54, Recruiting, M.D. Anderson Cancer Center | Trial completion date: May 2026 --> Jun 2028 | Trial primary completion date: May 2026 --> Mar 2028

Targeting dysregulated SPP1 improved cisplatin sensitivity and suppressed tumor invasion and metastasis in NRF2-hyperactivated HNSCC, underscoring the therapeutic potential of SPP1 inhibitors to improve patient outcomes.

These findings show that PYR functionally restores KEAP1-mediated NRF2 degradation of select NRF2Mut through a glue-like effect and overcomes therapy resistance in ESCC. Although the proposed glue-like mechanism remains hypothetical, this work supports further investigation into the NRF2-KEAP1 interaction and may inform the development of KEAP1-targeted strategies for NRF2Mut cancers, including ESCC.

P2, N=54, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2026 --> Apr 2027