Non-small cell lung cancer (nsclc) is a major lung cancer subtype and the leading cause of cancer mortality, with many patients deriving limited benefit from current systemic therapies. It is a clinically heterogeneous disease in which nrf2 activation-state stratification is relevant for therapeutic resistance, and elevated fgl1/TRIM21 protein ratio has been associated with poor prognosis. Recent work also highlights biomarker-defined subgroups such as MET fusion-positive disease with acquired resistance mutations, and lung squamous cell carcinoma, where ssx1 and trim58 were identified as independent prognostic factors. Therapeutic and translational studies in NSCLC include anti-PD-1 immunotherapy, the integrin beta-6-directed ADC sigvotatug vedotin, and an inhalable chemoimmunotherapy platform using doxorubicin. The disease is also a focus for computational and pathology advances, including the IGNITE multi-stain annotated digital pathology dataset and models predicting immunotherapy or PD-L1 outcomes from CT and histopathology. Overall, NSCLC research is increasingly centered on molecular stratification, immune microenvironment profiling, and resistance-aware treatment selection.
Immunotherapy and immune microenvironment
- A clinician-deployable deep hypergraph model integrating clinical and CT radiomics was developed to predict immunotherapy outcomes in NSCLC. (PMID:42008547)
- Targeting the IRF1-TRIM21 axis enhanced anti-tumor immunity by promoting ubiquitin-mediated degradation of fgl1 in NSCLC, supporting combination strategies with anti-PD-1 therapy. (PMID:42020516)
- SSX1 and TRIM58 expression stratified lung squamous cell carcinoma by tumor immune microenvironment characteristics and informed potential immunotherapy responsiveness. (PMID:42030005)
- Anti-PD-1 therapy was used as the immunotherapy backbone in NSCLC combination studies. (PMID:42020516)
Targeted therapy and resistance
- Liquid biopsy-based detection of acquired MET resistance enabled sequential targeted therapy in MET fusion-positive NSCLC. (PMID:42015375)
- The NRF2 readout beyond genotyping emphasized nrf2 activation-state stratification as clinically relevant in NSCLC. (PMID:41944556)
- Elevated fgl1/TRIM21 protein ratio was associated with poor prognosis in NSCLC, linking immune evasion to outcome. (PMID:42020516)
- Sigvotatug vedotin, an integrin beta-6-directed antibody-drug conjugate, showed dose-expansion results in advanced NSCLC. (PMID:42008777)
Pathology, imaging, and datasets
- A tissue- and cell-level annotated H&E and PD-L1 histopathology image dataset was introduced for NSCLC. (PMID:42009323)
- The IGNITE data toolkit was described as a multi-stain annotated NSCLC digital pathology dataset. (PMID:42009323)
- A multi-task masked autoencoder with GAN-based augmentation was developed for PD-L1 prediction from chest CT images in NSCLC. (PMID:42020694)
- H&E-stained slides were annotated for tissue compartments in primary and metastatic NSCLC to support computational pathology. (PMID:42009323)
Novel therapeutic platforms
- An inhalable Cryo-Shocked Tumor Cells platform was studied for synergistic chemoimmunotherapy in a lung cancer subtype context. (PMID:41947504)
- LNT-DOX showed superior tumor suppression in orthotopic lung cancer and pulmonary metastasis models. (PMID:41947504)
- Sigvotatug vedotin provided first-in-human phase I dose-expansion data in advanced NSCLC. (PMID:42008777)