STK11 mutation

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.

Within the major subgroups (G12A, G12C, G12D, and G12V), PD-L1 levels were not predictive of PFS. STK11 co-mutations were enriched in G12C, G12V, and other subtypes and were associated with shorter PFS.

KRAS mutant non-sq LA-NSCLC is associated with inferior outcomes, largely driven by increased distant and brain metastases. Tumors with concurrent CDKN2A and/or STK11 alterations had the poorest outcomes. These findings support the evaluation of KRAS inhibitors in this high-risk stage III population.

Restoring wild-type STK11/LKB1 in NSCLC lines with endogenous STK11/LKB1 loss reverses the ISR and reduces GDF15 expression rescuing the cachexia phenotype. Collectively, these findings implicate tumor-derived GDF15 as a key mediator and therapeutic target in STK11/LKB1-mutant NSCLC-associated cachexia.