STK11 mutation

STK11 mutations with KEAP1 or KRAS co-mutations are associated with significantly worse survival outcomes in mNSCLC compared with patients without these co-mutations. These findings underscore the urgent need for targeted therapies to improve prognosis in this high-risk population.

Whole-exome sequencing identified two novel heterozygous variants in POLE and EXO1. Intraoperative exploration of the terminal ileum is critical to avoid misdiagnosis and unnecessary colectomy.

The most frequently mutated genes were TP53, KRAS, EGFR, and STK11, with no significant differences between groups; ROS1 alterations were absent in STAS-negative tumors but detected more frequently in STAS-positive cases. Overall, these findings indicate that STAS positivity is associated with high-risk histological subtypes and advanced disease, suggesting its importance as a marker of tumor aggressiveness and emphasizing the need for its systematic evaluation in lung adenocarcinoma to better guide surgical planning and patient risk assessment.

RNA-Seq and DNaseI-Seq of these in vitro models and clinical samples identified upregulation of TGF-β signaling and EMT gene expression signatures, and corresponding changes in chromatin accessibility, in SMARCA4/STK11/KEAP1 triple mutant LUAD. We identify SMARCA4/STK11/KEAP1 triple mutant LUAD as a prognostically significant disease subset and nominate TGF-β signaling as a potential therapeutic target.

To determine combination partners that enhance RAS(ON) mutant-selective inhibition, a drug repurposing screen revealed that KRASG13C models are selectively vulnerable to chemotherapy. Combination of docetaxel with RMC-8839 demonstrated robust anti-proliferative activity in KRASG13C-driven NSCLC models in vitro and in vivo.

p53 IHC, particularly using a ≥40% cut-off at 3+ intensity, is an accurate and accessible surrogate for TP53 mutation detection in LUAD patients. This method facilitates rapid molecular stratification, optimal resource utilization and informed prognostic and therapeutic decision-making in routine pathology practice.

P1/2, N=30, Not yet recruiting, Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

The isolated mouse cell line provides a powerful platform for basic and translational EC studies, matching well with the corresponding in vivo models. The fidelity of the cell line to human-relevant genetic alterations and tumor biology makes it a valuable tool for investigating EC pathogenesis and evaluating novel therapeutic approaches.

KRAS Q61H and Q61L were the predominant mutational subtypes and demonstrated distinct molecular and clinical characteristics, with differences in co-mutational landscape and survival differences. Immunotherapy-based regimens were associated with more favorable outcomes compared to chemotherapy, particularly in patients with high PD-L1 expression, underscoring the importance of subtype-specific molecular characterization in clinical decision-making.

Collectively, our analysis describes the driver genes and mutation characteristics in SCC. The multi-cohort and network-based framework employed in this study identifies candidate hub genes that warrant further clinical investigation in cervical cancer.

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

P=N/A, N=79, Recruiting, Memorial Sloan Kettering Cancer Center