Lung Adenocarcinoma

P3, N=220, Recruiting, Sun Yat-sen University | Not yet recruiting --> Recruiting

P2, N=50, Recruiting, Emory University | Trial completion date: Sep 2028 --> Sep 2029 | Trial primary completion date: Mar 2028 --> Mar 2029

In parallel, circSMAD4 formed a specific ribonucleoprotein complex with the m6A reader IGF2BP2, facilitating IGF2BP2 association with COL4A1, ACTA2, and SPI1 transcripts and enhancing their m6A-dependent stability. Together, these dual branches converge on a matrix-remodeling output, positioning circSMAD4 as a post-transcriptional hub that reinforces protumor TAM programs in LUAD and a potential target for microenvironment-directed therapy.

ATAD2 drives immunotherapy resistance in LUAD by activating an ATAD2-LDHA-LA axis that impairs CD8+ T cell function. Targeting ATAD2 may broadly restore antitumor immunity and enhance the efficacy of T cell-based immunotherapies.

Although less potent than the nanomolar-range reference drug Epothilone B (IC50 < 0.1 μM), rugulosin A showed submicromolar-to-low micromolar efficacy with notable selectivity toward cancer cells, which is considered significant for an unoptimized natural product scaffold. Its antiproliferative activity against K562 cells (GI50 = 3.69 μM), benchmarked against Imatinib (GI50 = 0.373 μM), also falls within the active range of natural product leads...Molecular docking revealed strong binding energies (-10.1, -9.8, and -11.0 kcal/mol), along with a stable molecular dynamics simulations data. These findings highlight rugulosin A (3) as a promising anticancer lead that modulates major apoptosis signaling pathways.

Our findings identify the KIF18B/KIF20A/KIF2C/KIF4A/KIFC1/TMPO-AS1/E2F1/hsa-let-7b-5p regulatory axis as a potential therapeutic target in LUAD, particularly among high-risk smokers. This suggests that its regulatory mechanisms could lead to new targeted therapies.

This study systematically revealed a PANoptosis core gene network centered on M2 macrophages in LUAD, elucidating a new mechanism by which ginsenosides induce integrated cell death by regulating this network. This provides new potential targets and theoretical basis for the immunotherapy of LUAD and the development of traditional Chinese medicine monomers.

Our findings redefine epigenetic regulation in LUAD, demonstrating that regional methylation patterns-not global promoter status-orchestrate oncogene activation. We propose a novel framework for spatially resolved methylomics, advocating 1) dual-target assays monitoring both promoter and gene body methylation to improve diagnostic precision, and 2) therapeutic exploitation of SHOX2's intronic methylome as a druggable epigenetic switch.

Concurrent targeting of PI3K and IR/IGF-1R signaling effectively overcomes adaptive resistance in PIK3CA-mutant NSCLC, supporting the rationale for further clinical evaluation of this combined therapeutic strategy.

Germline mutations constitute a minority of NSCLC cases but carry important prognostic, predictive, and preventive implications. Systematic germline testing in selected patients, particularly those with early-onset disease, strong family history, or tumor sequencing suggestive of hereditary variants, could guide precision oncology, enable targeted treatments, and facilitate familial risk management.

P2, N=162, Recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Not yet recruiting --> Recruiting