STK11 mutation

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.

This study validates the primary drivers of cervical adenocarcinoma and reveals novel findings, including notable racial disparities in TP53 mutation frequency and unique patterns of co-occurring mutations. These findings highlight the genomic heterogeneity of the disease and suggest that ancestry and tumor evolution may influence its molecular pathogenesis, offering potential avenues for the development of targeted therapies and personalized biomarkers.

Ovary metastasis reflected advanced disease burden and surgery might be associated with improved survival in advanced stage. For genomic information, GEA showed genetic heterogeneity and a low level of genomic instability.

Genetic alterations promote tumor immune evasion, facilitating cancer development and progression. Continued advances in air quality control, molecular diagnostics, and precision therapies are essential for prevention, early detection, and reduction of the global disease burden.

Finally, in an activating NRAS-mutant (p.Q61R) HG-ESS xenograft, the combination of MEK and FAK inhibition dramatically suppressed tumor growth and prolonged survival, highlighting a promising targeted treatment strategy. Overall, our comprehensive analysis defines the molecular basis of ESS and provides a strong preclinical rationale for precision therapies in this aggressive cancer.

This approach resulted in unprecedented survival outcomes: the 72-month overall survival dramatically exceeds the median OS of less than 12 months reported for advanced PSC, and the patient maintained a progression-free survival of over 37 months on combination therapy, surpassing historical PFS benchmarks. This case provides a clinically actionable framework for managing multi-driver mutated, immunoresistant PSC.