KRAS wild-type

Multiplex immunofluorescence staining demonstrated that BCL-xL inhibition effectively triggered apoptosis in heterogeneous PDX tumor slice models, including models harboring oncogenic BRAF mutations. Our findings suggest that cetuximab-resistant CRC retains apoptotic competence, and that BCL-xL inhibition serves as a robust alternative therapeutic strategy that is largely independent of the tumor mutational profile.

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.

P1/2, N=178, Not yet recruiting, Shanghai Eastern Hospital; Nerviano Medical Science Shanghai Ltd.

P1/2, N=120, Recruiting, Shanghai East Hospital; Novatim Immune Therapeutics (Zhejiang) Co., Ltd.

Conversely, KRAS-wild-type cells preserve NAD+ influx via sufficient baseline succinyl-SLC25A51, which stabilizes SLC25A51 and enables sufficient succinate accumulation to drive hypoxia inducible factor 1 subunit alpha (HIF1α)-mediated compensatory NAD+ production during treatment. Our work reveals a KRAS-specific metabolic vulnerability and proposes a dual-inhibition therapy for KRAS-driven AML.

P1, N=194, Recruiting, Hefei TG ImmunoPharma Co., Ltd.

These hydrogen bonds not only strengthen the hydrophobic contacts at the monobody-KRAS interface but also correct the abnormal conformational equilibrium and restore the disrupted allosteric circuitry. Overall, our findings confirm that D12 is a structurally and functionally validated anchor for the development of next-generation inhibitors targeting G12D KRAS-driven malignancies.

Within surgically treated patients, baseline CA19-9 emerged as the most informative prognostic marker, while traditional clinicopathologic variables showed limited discriminatory value. These findings highlight the importance of careful patient selection and support further prospective studies integrating molecular and biomarker-based strategies to refine prognostication and optimize surgical decision-making in RAS-WT mCRC.

Ion Chiricuta" between 2015 and 2024 with first-line FOLFOX/FOLFIRI plus panitumumab...In multivariate analysis, only bNLR remained independently associated with PFS. These results suggest that both baseline and dynamic NLR may serve as low-cost prognostic biomarkers in mCRC patients treated with anti-EGFR therapy.

For the first time, we propose a novel combined score integrating NO, arginase, SII, and SIRI as simple, accessible, and non-invasive prognostic and predictive markers. Our findings may open new avenues for patient stratification and treatment optimization in precision oncology research.

Emerging clinical evidence supporting the use of ICIs in selected patients across neoadjuvant, adjuvant, and advanced disease settings is also reviewed, along with challenges related to assay discordance, tumor heterogeneity, and immunotherapy resistance. Finally, future directions are highlighted, emphasizing the need for standardized testing algorithms, integration of multi-omics and spatial profiling technologies, and prospective clinical studies to optimize precision treatment strategies for this rare but clinically meaningful subtype of pancreatic cancer.

Concomitant treatment with, N-acetylcysteine reversed cell death response induced by investigated compounds (75.7 ± 15.1 % and 33.1 ± 9.9 % in average for MCF7 and A549 cells, respectively), suggesting that the generation of reactive oxidative species (ROS) was the key trigger of the cell death...Additionally, ultrastructural analysis confirmed significant mitochondrial damage in both cell lines. Investigated compounds potently disrupt mitochondrial function and can serve as a valuable asset for testing capacity of new antioxidant agents.