NFE2L2 mutation

NFE2 gene mutations in MPNs were predominantly frameshift mutations. NFE2 gene mutations were correlated with older age, elevated levels of several inflammatory factors (including TNF-α、IFN-γ、IL-10、IL-12P70、IL-17) , and they mostly occurred in late-stage of MPNs.

P1, N=22, Active, not recruiting, National Cancer Institute (NCI) | N=85 --> 22 | Trial completion date: Jun 2026 --> Nov 2026 | Trial primary completion date: Jun 2026 --> Nov 2025

In PD-L1 TPS ≥ 50% NSCLC patients treated with pembrolizumab, our results suggest an improved PFS in patients predicted to be KEAP1/NFE2L2 mutated.

P1, N=41, Terminated, Novartis Pharmaceuticals | N=140 --> 41 | Trial completion date: Jul 2027 --> Oct 2025 | Recruiting --> Terminated | Trial primary completion date: Jul 2027 --> Oct 2025; The trial was terminated due to a business decision and not as a result of any safety concerns

These findings support integrating multiple biomarkers to improve risk stratification and personalize treatment in unresectable stage III NSCLC. The study is registered on www.clinicaltrials.gov (ClinicalTrials.gov identifier: NCT04392505).

Lastly, we utilized one small molecule inhibitor, SMARCA2-IN-8, to inhibit progression of Keap1-deficient NSCLC murine models. Together, our study highlight the synthetic lethal relationship between Keap1 and PHF10, and provide targeting PHF10-SMARCA2 complex as an effective option to hit Keap1-deficient NSCLC.

NFE2L2 mutations were more common in the middle thoracic esophagus, appeared to be associated with tumor progression, and were linked to poor prognosis.

Furthermore, pharmacological inhibition of NRF2 signaling may overcome cisplatin resistance in high-risk patients with NFE2L2-mutant tumors. While the signature shows significant clinical potential, further independent validation is required before it can be adopted into routine clinical practice. We developed a robust nine-gene prognostic model for predicting Progression-Free Survival (PFS) in CC, which provides novel insights into HPV-associated oncogenesis and facilitates risk stratification and therapeutic decision-making in CC management.

This case provides molecular evidence that a TP53 mutation, even at a low burden, may contribute to leukemic progression of a chronic phase myeloproliferative neoplasm (MPN). These observations increase our understanding of the pathophysiologic behavior of TP53 mutations and underscore the importance of further causal research towards the clinical implications of these mutations in chronic phase MPN.

We demonstrate unique metabolic dependency of β-catenin-mutated HCCs on GS in tumor cells which is diverted to macrophages upon GS elimination in tumor cells. This adaptation alters macrophage metabolism and function leading to compromised immunosurveillance and greater tumor burden. Our study reveals a metabolic dynamic between HCC cells and macrophages with impact on tumor biology.

Experiments in KEAP1-mutated cells and omics data from a panel of cell lines indicated that PD-L1 mRNA/protein levels are not dictated by constitutive NRF2 activation in vitro. These results advance our understanding of the tumor microenvironment diversity in NSCLC with hyperactive NRF2 and offer a potential histology-based method to identify ICI responders within this subset.

Gene expression profiling revealed shared and unique NRF2 transcriptional programs between these models, some of which were shared in primary lung tumors. Collectively, our findings reveal context-dependent effects of NRF2 activation on the growth and differentiation state of two human NSCLC models, supporting a role for NRF2 activation in altering the differentiation of human NSCLC during tumor progression.