EGFR wild-type

A 3D blood-brain barrier-glioblastoma model was used to optimize the starting dose. Our translational strategy addressed regulatory feedback received from the Danish Health and Medicines Agency (DKMA) and the FDA to further increase confidence in the applied in vitro approach and ultimately led to the regulatory approval of our Ph1 study protocol across multiple countries.

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

Moreover, extracellular application of bulky EGFR binders suppressed resistant mutants by disrupting oligomerization. These findings highlight steric disruption of EGFR oligomerization as a promising strategy for overcoming therapy resistance in NSCLC and introduce a versatile screening platform for developing competitive and allosteric inhibitors.

MTT assay showed that 6 and 9b were 4.5 and 2 times more potent than doxorubicin against MCF-7 cells, while 9a and 13b were 10 and 7.5 times more effective against MDA-MB-231 cells, respectively...Compound 13b exhibited comparable EGFRL858R inhibition to lapatinib and outperformed pictilisib against PI3Kα, PI3Kβ, and PI3Kδ. Compound 6 showed greater ARO inhibition than letrozole, while being slightly less potent than pictilisib against PI3Kα and PI3Kβ...Docking studies supported the in vitro enzymatic inhibition assays results. Thus, 9b and 13d are potent anti-breast cancer benzoxazoles with selective ARO and PI3kα inhibition activity, respectively, while 6, 9a, and 13b are multi-target inhibitors exhibiting other anticancer synergistic mechanisms.

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.

Primary and acquired MET mutations in NSCLC exhibit distinct genomic characteristics. Patients harboring concurrent EGFR mutations in NSCLC may derive less benefit from MET-TKI and ICI, whereas those harboring TP53 co-mutations tend to experience more favorable outcomes compared with TP53 wild-type NSCLC patients when treated with MET-TKI.

Furthermore, evaluation of 7c in HCC827 (exon 19 deletion) mutation, which is a cell model highly sensitive to tyrosine kinase inhibitors, showed that the tested compound exhibited lower inhibition than erlotinib...Furthermore, 7c caused an increase in the levels of caspase 3 (4.68 folds) and caspase 9 (4.54 folds) in HCT-116 cells. Additionally, in silico studies of 7c showed a plausible binding mode that correlates with its potent inhibitory activity against the two enzymes, whereas ADME prediction revealed a favorable oral absorption.

Most patients preferred atezolizumab SC regardless of baseline characteristics, mean injection duration, and cumulative number of SC injections. The trend for a stronger preference was higher among patients who preferred SC than those who preferred IV. Our findings suggest that the proportion of preference for atezolizumab SC over IV is highest in patients aged > 74 years, and that administrator's experience could be an important factor influencing patient preference.

Several molecular mechanisms that can drive SCLC transdifferentiation have been identified. The treatment of transdifferentiated SCLC remains a significant challenge, although promising new strategies are currently under investigation. This review summarizes the current understanding of SCLC transdifferentiation.

P3, N=594, Active, not recruiting, AstraZeneca | Trial completion date: Oct 2025 --> Oct 2026

P1/2, N=22, Completed, Laekna Limited | Active, not recruiting --> Completed

Furthermore, patients with EGFR-mutant lung adenocarcinoma undergoing treatment with EGFR tyrosine kinase inhibitors exhibited a significantly extended survival rate compared with those with wild-type EGFR receiving chemotherapy. In conclusion, the present study demonstrated that immunohistochemistry with pleural effusion cell blocks can aid in clarifying the histological subtype of lung cancer, and enable EGFR mutation detection, which can effectively guide molecular targeted therapy.