STK11 mutation

P2, N=95, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Nov 2027 --> Dec 2026

Collectively, we associated the redox status mediated by loss-function mutations of KEAP1 or STK11 to immune evasion and immunotherapeutic resistance by suppressing STING/MDA5 expression and interferon signaling of cancer cells. Our findings link redox homeostasis to STING/MDA5 expression and tumor immunogenicity, raising the possibility that targeting this axis could represent a future strategy to enhance ICI efficacy.

Moreover, SMARCA4 deficiency leads to poor responses to immunotherapy, potentially due to core metabolic disorders, inactivation of tumor suppressor signaling, and immune suppression in the tumor microenvironment. These findings suggest that treatment strategies should be adjusted to address these molecular mechanisms.

P1, N=40, Recruiting, University Health Network, Toronto | Trial primary completion date: Dec 2025 --> Aug 2026

In KRAS-mut NSCLCs with or without STK11/KEAP1 mutations, the GPAs in the DNA-binding genes ARID1A/ARID2 affected the outcomes of immunotherapy, possibly through the downregulation of STING expression.

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.