KEAP1 mutation

We also demonstrate that loss of KEAP1 reduces sensitivity of RET fusion-positive cells to selpercatinib, consistent with previous reports that these alterations promote drug resistance in other malignancies. In this study, we comprehensively profile KEAP1 mutations in thyroid tumors, showing that they are more prevalent and functionally significant than previously recognized. These findings position KEAP1 mutations as novel oncogenic variants in thyroid cancer and support the integration of KEAP1/NRF2 pathway profiling into future studies and clinical frameworks.

Prevalence of secondary RET mutations after SRIs was low, underscoring greater role for off-target resistance. Recurrent acquired alterations involving tumor suppressor genes or upstream regulators of MAPK and PI3K pathways were identified, most commonly MET amplification. Continued efforts to characterize SRI resistance biology are critical to guide development of novel therapeutic strategies.

As an interpretable model integrating readily-accessible and crucial clinical-genomic predictors, PRIME achieves enhanced performance, allowing for early outcome prediction, refined risk stratification, and personalized clinical decision-making.

In contrast, NRF2 activators, such as bardoxolone methyl (CDDO-Me), sulforaphane, and dimethyl fumarate, exhibit chemopreventive effects by enhancing detoxification and mitigating oxidative DNA damage during early tumorigenesis...Therefore, understanding the temporal and contextual effects of NRF2 signaling is crucial for therapeutic design. The aim of this review is to examine how pharmacological modulation of NRF2 influences the invasive and metastatic dimensions of tumor progression, in addition to discussing its potential integration into TNM-based prognostic and treatment frameworks.

In this large, multicenter Turkish real-world cohort, the TGA spectrum broadly mirrors global patterns while revealing local nuances; EGFR mutations were more frequent than expected in SCC, and nationwide NGS adoption is accelerating. Limitations include retrospective design, non-centralized PD-L1 testing, and missing data. Prospective, standardized studies integrating outcomes and resistance mechanisms are warranted to refine regional precision oncology.

Similarly, subcutaneous KEAP1 KO tumors were larger and more immune-suppressed compared to WT tumors. Both CDDO-Me and omaveloxolone reduced the tumor burden and improved immune cell phenotypes within the TIME independent of KEAP1 mutational status.

Collectively, available evidence from various studies positions multi-omics profiling as a critical clinical tool. It enables the classification of tumors by dominant immunometabolic phenotype, thereby paving the way for biomarker-driven trials that rationally combine metabolic inhibitors with immunotherapy to overcome resistance.

Although promising, most biomarkers require prospective validation in large, uniformly treated cohorts. Integrative strategies-particularly when combined with AI-driven analytics-hold potential to refine patient stratification and guide clinical use of ICIs in NSCLC.

Detailed smoking history provides crucial insights for optimizing IO selection in advanced NSCLC through mechanistic alterations in both the tumor microenvironment and systemic plasma protein profiles.

KRAS G12V-mutated NSCLC is characterized by a strong association with tobacco use, high co-mutation rates in clinically relevant genes, and a favorable response to PD-L1-based immunotherapy. The observed mutation landscape supports the potential for dual checkpoint blockade in a significant subset.

Rats were assigned into six groups (n = 8, each): (I) normal (control), (II) gastric ulcer induced with a single oral dose of indomethacin (30 mg/kg body weight), (III) rats received oral simvastatin (40 mg/kg/day) for 14 days, (IV) rats received oral ezetimibe (10 mg/kg/day) for 14 days, (V) the combination group received both oral simvastatin and ezetimibe, and (VI) standard group received oral famotidine (20 mg/kg). Simvastatin plus ezetimibe exerted synergistic gastroprotective effects in rats, associated with Nrf2/HO-1 activation and suppression of Keap1, oxidative stress, and pro-inflammatory cytokines. This combination may represent a novel therapeutic approach for preventing NSAID-induced GUs, meriting further mechanistic and translational studies.

Collectively, we associated the redox status mediated by loss-function mutations of KEAP1 or STK11 to immune evasion and immunotherapeutic resistance by suppressing STING/MDA5 expression and interferon signaling of cancer cells. Our findings link redox homeostasis to STING/MDA5 expression and tumor immunogenicity, raising the possibility that targeting this axis could represent a future strategy to enhance ICI efficacy.