STK11 mutation

A novel EGFR mSig that captures the transcriptional footprint of EGFR activation revealed a subset of EGFR WT LUADs with "mt-like" features. mSig refines LUAD taxonomy beyond mutation-only pie-chart models by incorporating lineage and co-mutation context. Lineage-directed stratification with co-alteration identifies clinically relevant groups across EGFR and RAS states and highlights new treatment opportunities for patients currently considered "oncogene-negative.".

Case 1 harbored a truncal KRAS p.G12C mutation with high-level amplification of chromosome 11q13-q14, including CCND1, and demonstrated a clinical response to sotorasib...These findings highlight the molecular heterogeneity of Rb-retained SCLC and demonstrate that this subgroup can harbor clinically actionable oncogenic drivers. Accordingly, routine assessment of Rb expression in SCLC, followed by comprehensive molecular profiling of Rb-retained tumors, is warranted to uncover therapeutically relevant targets.

P2, N=8, Completed, NYU Langone Health | Recruiting --> Completed | N=14 --> 8 | Trial completion date: Dec 2026 --> Nov 2025 | Trial primary completion date: May 2026 --> Nov 2025

In contrast, SMAD4 and SMAD2 showed frequent loss-of-function-type alterations in GAS, including copy-number loss, but were not detected in LEGH. These findings provide insights into the genomic landscapes of LEGH and GAS and suggest potential molecular markers for this transition, which may inform future diagnostic and therapeutic research.

This review summarizes the associations between genetic mutations and metastatic sites, explores underlying molecular mechanisms, and discusses mutation-based risk prediction and personalized therapeutic strategies. With multi-omics integration and further clinical research, genetic profiling may become a key tool for guiding metastasis prevention, early intervention, and treatment optimization in NSCLC.

STK11 mutations are associated with poor responses to ICI in other cancers, and elucidating the role of STK11 in cervical cancer may improve targeted and immunotherapies. Characterized one of the largest cohorts of fresh-frozen, invasive cervical cancer cohorts and documented that STK11 mutations and deletions are more prevalent in adenocarcinoma, and defined an early-onset, more aggressive subtype.

Given the aggressive nature and poor prognosis of untreated SMARCA4-dNSCLC, timely diagnosis and multimodal treatment are essential to improving survival. Further prospective studies are needed to optimize management strategies.

TP53-d and STK11 mutations might have a predictive impact in localized-stage NSCLC, but further investigation is needed. KEAP1 mutations associate with worse outcomes, especially in patients receiving adjuvant chemotherapy.

TTF-1 negativity identifies a subset of LUAD with worse outcomes to immunotherapy, chemo-immunotherapy, and KRASG12C inhibitors.

P=N/A, N=1368, Recruiting, Icahn School of Medicine at Mount Sinai | Trial completion date: Nov 2033 --> Jan 2033 | Trial primary completion date: Nov 2033 --> Jan 2033

Rational combination strategies that pair genomic-targeted agents (sotorasib and adagrasib) with metabolic inhibitors (CB-839 and TVB-2640) show promise in overcoming adaptive resistance. Integrating genomic and metabolic profiling may enhance precision oncology approaches and improve clinical outcomes.

The interpretable DeepSurv model, integrating multimodal features, enables quantitative survival prediction and risk stratification in advanced NSCLC, facilitating personalized decision-making.