STK11 mutation

The future of immunotherapy in NSCLC will likely be premised on a holistic understanding of tumor biology, immune dynamics, and host characteristics. Such an integrated approach is key to overcoming current limitations, enabling personalized strategies, and broadening the clinical benefit of immunotherapy to a wider patient population.

Dynamic and active immune recruitment, indicated by immune-hot TME and high TLS score, was predictive of ICI benefit in patients with LUAD. Further prospective studies are warranted to expand to other treatment combinations with PD-(L)1 inhibitors.

In conclusion, SDTTs exhibited a high rate of skeletal muscle metastases. Skeletal muscle metastases and first-line chemoimmunotherapy were independent prognostic factors for OS in SDTTs.

While significant progress has been made, refining biomarker-driven selection and optimizing combination sequencing remain paramount. This thorough synthesis highlights promising future directions to overcome these hurdles and improve long-term survival in NSCLC.

PA-MSHA improved immune cells function and enhanced their antitumor effects against STK11 mutant NSCLC, which was associated with the activation of the STING pathway.

In this single-center, real-world, retrospective analysis, among the 38 patients with advanced NSCLC receiving KRAS G12C inhibitors, a never or light smoking history, poor performance status, and the presence of tumor pathogenic KEAP1 mutations were associated with worse clinical outcomes. Within the limitations of the study, clinicians should consider these variables when formulating treatment for KRAS G12C-mutant NSCLC.

P2, N=54, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2026 --> Apr 2027

Mechanistically, STK11 loss drove tumor-derived C3 production and downstream CXCL2 and complement factor H (CFH) production that promoted immune evasion and impaired anti-PD-1 efficacy. Our results show a C3-driven signaling axis for STK11-mutant LUAD promoting immune evasion and identifies therapeutic targets to render these tumors sensitive to anti-PD-1.

The description of similar tumors harboring STK11 mutations has opened new pathways in understanding these tumors. In this review, we sought to present in detail the reported FATWO and STK11 adnexal tumors to understand their clinical and pathological features, and to discuss their differential diagnosis.

KRAS mutations represent the most prevalent oncogenic drivers in non-small cell lung cancer (NSCLC), defining a clinically heterogeneous subset that was historically considered "undruggable." The identification of a mutant-specific allosteric pocket in KRAS G12C led to the development of sotorasib and adagrasib, fundamentally altering the treatment paradigm for pretreated patients...This review provides a comprehensive synthesis of the expanding therapeutic landscape, moving beyond G12C-selective inhibition toward next-generation allele-specific agents, such as G12D inhibitors, and groundbreaking pan-RAS/RAS(ON) tri-complex inhibitors like RMC-6236...As the field transitions from single-allele blockade to multi-selective RAS(ON) inhibition and rational vertical pathway targeting, personalized, biomarker-guided treatment algorithms will be essential. By outlining the trajectory from G12C to pan-RAS strategies, this review captures the evolving precision oncology framework necessary to achieve durable clinical benefit in KRAS-mutant NSCLC.

Mechanistically, the abrogation of the binding between CRTC2 and CREB was sufficient to restore sensitivity to immunotherapy. These findings provide critical insights into the central role of CRTC2 in modulating response to ICB and identify the disruption of CRTC2-CREB interaction as a potential therapeutic approach for this patient population.

Except for age, histologic diagnosis, and liver metastasis, long-term survival is not correlated with baseline variables. Approximately a quarter of progress after 2 years of disease control.