AGER (Advanced Glycosylation End-Product Specific Receptor)

A preliminary association between decreased sRAGE and overall survival in SCLC patients was observed. Serum sRAGE shows potential as a blood-based biomarker reflecting metabolic, immune, and inflammatory status in lung cancer, warranting further investigation to clarify its prognostic and therapeutic relevance.

These findings demonstrate that LPS tolerance promotes an atheroprotective macrophage phenotype characterized by attenuated inflammatory signaling and enhanced cholesterol efflux. However, this protective immunometabolic program is selectively disrupted by AGE exposure, highlighting a critical interface through which chronic metabolic stress may override innate immune tolerance and contribute to atherosclerotic progression.

This study reveals causal proteins for various lung cancer phenotypes and complications, emphasizing causal pathways and potential therapeutic targets for lung cancer and providing new insights into its etiology, prevention, treatment, and therapy.

Here, we summarize these mechanisms, including both immunostimulatory and immunosuppressive DAMPs, and review key DAMP receptors-such as TLRs, NLRs, cGAS, and advanced glycosylation end-product-specific receptor (AGER)/RAGE-along with their downstream signaling cascades. Finally, we highlight emerging strategies to modulate DAMP signaling for cancer immunotherapy and the treatment of inflammatory diseases.

Among the 13 identified druggable targets, RPL14 and AGER showed therapeutic potential as approved or investigational drugs targeting these proteins. These findings offer new insights into the pathogenesis of LC and potential therapeutic targets.

Analyzing three external GEO datasets confirmed that TLR4 and AGER expression increased in IBC compared to non-IBC samples. Overall, IBC samples showed higher TLR4 and AGER expressions than other breast cancer types, shedding light on the significance of these markers on IBC biology.

Through the comprehensive application of MR analysis and Bayesian colocalization analysis, we have successfully identified that EVI5, OGA, and TNFRSF14 may be key therapeutic targets for MS. These findings may provide a scientific basis for the development of novel immunotherapies, combination treatment regimens, or targeted intervention strategies.

Despite the steep Trendelenburg position of the RSC group inciting more pulmonary stress, inflammation and lung epithelial injury, as indicated by higher sRAGE, it demonstrated a lower PPCs occurrence relative to its DAC counterpart, with a slightly inclined or reversed Trendelenburg position. None of the plasma biomarkers of inflammation or lung injury indicated sufficient prognostic value for PPCs.

MRTX1133 is a highly selective and first-in-class KRAS-G12D inhibitor under clinical development...This combination therapy also induces high-mobility group box 1 (HMGB1) release, resulting in a subsequent antitumor CD8+ T cell response in immunocompetent mice. Collectively, the study findings underscore the potential to enhance the efficacy of KRAS-G12D blockade therapy by targeting AGER-dependent macropinocytosis.

P=N/A, N=40, Recruiting, Assistance Publique Hopitaux De Marseille | Not yet recruiting --> Recruiting | Trial completion date: May 2026 --> Dec 2026 | Initiation date: Feb 2024 --> Aug 2024 | Trial primary completion date: Feb 2026 --> Aug 2026

However, a positive association was observed for sRAGE. Our findings may stimulate further research on the role of AGEs and sRAGE in survival among cancer patients with special emphasis on potential effect modifications by sex and diabetes.

Only rs2070600, which enhances RAGE function by inducing a Gly82Ser polymorphism in the ligand-binding domain, was associated with MACE. The lack of associations with incident MACE for the other sRAGE-lowering SNPs suggests that this functional RAGE modification is central for the observed relationship.