STK11 mutation

Emerging evidence supports rational combination strategies, including parallel inhibition of epidermal growth factor receptor, protein tyrosine phosphatase non-receptor type 11 or SOS1 and vertical blockade of the mitogen-activated protein kinase-extracellular signal-regulated kinase or phosphatidylinositol 3-kinase-mechanistic target of rapamycin cascades; immunotherapies such as checkpoint blockade, T-cell receptor (TCR)-T cells, bispecific T-cell engagers or cytokine-armed oncolytic viruses; metabolic interventions targeting macropinocytosis or autophagy; as well as radiotherapy...Precision approaches that integrate multiomics profiling with longitudinal circulating tumour DNA analysis enable biomarker-guided patient selection (eg, based on STK11 and KEAP1 comutations) and support therapeutic adaptations, including sequencing strategies and intermittent dosing. Thus, network-level KRAS interception combined with biomarker-driven, clonal evolution-informed trial design offers a path towards sustained control of KRAS-driven cancers.

Our multi-source imaging-genomic-clinical model accurately predicts the risk of recurrence after surgery in stage ⅠA1-ⅢA NSCLC patients and can be used for risk stratification to guide clinical follow-up management and postoperative treatment strategies.

AXL expression is associated with reduced immunotherapy efficacy in NSCLC and may serve as a predictive biomarker and therapeutic target.

Furthermore, among Stage 4 cases, while all STK11 mutation types result in decreased overall survival probability compared to the STK11 wild-type cohort, the effect appears most pronounced among the STK11-loss/KRAS-mutant group. These findings underscore the heterogeneity of STK11-mutant NSCLCs and highlight the opportunity for further investigation into specific STK11 mutation subtypes in guiding prognosis and therapeutic decision making for individuals with lung cancer.

These findings underscore the therapeutic potential of PARP inhibitors in high-LOH MTMCT while highlighting the emergence of resistance mechanisms, including CN-LOH and loss of EMSY amplification. They emphasize the importance of considering tumor evolution and treatment timing when interpreting CGP results, providing a foundation for further research into predictive biomarkers and resistance mechanisms in rare gynecologic malignancies.

In 10/18 cases, mutational signature analysis revealed a dominant smoking signature, providing evidence of lung origin. Our findings unveil diagnostic pitfalls that may warrant additional evaluation to avoid misdiagnosis of metastatic lung carcinoma as a primary breast carcinoma.

Both cases were managed with capecitabine-oxaliplatin plus bevacizumab, followed by maintenance therapy, achieving disease stabilization for at least 9 months. Given the rarity of STM, especially in metastatic or recurrent settings, there is an urgent need for standardized diagnostic protocols and evidence-based treatment strategies. These cases support the use of tumor-specific chemotherapy regimens guided by the histological and molecular characteristics of STM.

Approximately 280 eligible patients, aged ⩾18 years, will be randomized 1:1 to receive tremelimumab 75 mg plus durvalumab 1500 mg plus carboplatin AUC 5/6 or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 every 3 weeks (Q3W) for four cycles, followed by maintenance durvalumab 1500 mg plus pemetrexed 500 mg/m2 Q4W, with an additional dose of tremelimumab 75 mg at week 16 and optional further dose at month 24; or pembrolizumab 200 mg plus carboplatin AUC 5/6 or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 Q3W for four cycles, followed by maintenance pembrolizumab 200 mg plus pemetrexed 500 mg/m2 Q3W. Results will help to inform clinical practice and establish a biomarker-driven treatment strategy for these subtypes of mNSCLC with high unmet need. ClinicalTrials.gov identifier: NCT06008093 (registration date: August 17, 2023).

Unsupervised clustering of radiomics features revealed two distinct groups separated by entropy features, of which the entropy-rich cluster was associated with STK11 mutations. Our study demonstrates that integrating radiomics with localized genomic analysis enhances the understanding of tumoral heterogeneity and may improve the targeting of advanced tumor regions for diagnostic sampling.

These findings support integrating multiple biomarkers to improve risk stratification and personalize treatment in unresectable stage III NSCLC. The study is registered on www.clinicaltrials.gov (ClinicalTrials.gov identifier: NCT04392505).

Pathway enrichment pointed towards coagulation-associated processes as the principal biological context for FGB up-regulation. Collectively, these findings identify elevated FGB as a hallmark of an aggressive smoker-derived LUAD subset and as a standalone prognostic biomarker, offering potential value for risk stratification and therapeutic decision-making in this patient population.

P2, N=60, Not yet recruiting, Yueyang Central Hospital; Yueyang Central Hospital