EGFR L858R

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.

P2, N=150, Active, not recruiting, Myung-Ju Ahn | Trial completion date: Jul 2025 --> Dec 2026 | Trial primary completion date: Mar 2025 --> Mar 2026

Aumolertinib plus anlotinib was effective and well-tolerated as first-line therapy in EGFR-mutant NSCLC patients with BMs. Trial Registration: ClinicalTrials.gov(identifier NCT04978753, registered July 20, 2021).

A plasma sample serves as a supplement for identifying GPS when a tissue sample is unavailable. Moreover, the integration of FISH, NGS, and ddPCR provided a comprehensive assessment of MET amplification.

In participants with atypical EGFR-mutated advanced NSCLC, amivantamab-lazertinib demonstrated clinically meaningful antitumor activity with no new safety signals.

Both almonertinib and osimertinib demonstrated good efficacy in patients with brain metastases, and PD-L1 expression was not associated with the prognosis of EGFR L858R mutant NSCLC. Finally, no significant difference between osimertinib and almonertinib for the treatment of patients with EGFR L858R mutations was observed. Both options remain viable for these patients.

Compared with perfectly matched gRNAs, the strategic incorporation of mismatches into gRNAs enhanced editing specificity for single-base mutant alleles. Our findings substantially improve the precision and safety of CRISPR-based genome editing for cancer therapy, particularly in cases involving mutant alleles.

These alterations were mutually exclusive with common drivers such as EGFR or KRAS. Detection of rare fusions highlights the therapeutic potential of comprehensive NGS profiling in Romanian NSCLC patients.

Patients received RAM (10 mg/kg every 2 wk) plus GEF (250 mg once daily) until disease progression (period 1); patients with disease progression who acquired a T790M mutation received RAM plus osimertinib (80 mg once daily) (period 2). Treatment-emergent T790M rate post progression was 81.3%. RELAY+ revealed a favorable benefit-risk profile for RAM plus GEF in East Asian patients with untreated EGFR-mutated metastatic NSCLC, supporting RAM plus GEF as an alternative first-line treatment option, particularly in those with an L858R mutation.

In the ITT population, we found no differences in OS between amivantamab-lazertinib and osimertinib-chemotherapy, despite a slightly higher PFS of the latter. Osimertinib-chemotherapy could be more effective in patients with CNS metastases, without liver metastases, and EGFR L858R mutation, however we could not compare OS in these subgroups. Due to the indirect nature of the comparison and the limitation of the methods our results are not definitive, but rather hypothesis-generating. Other factors must be considered in the choice of the treatment, including patient's characteristics, the safety profile of the combinations, and center's facilities and expertise.

Autophagy inhibition by 3-methyladenine and ATG gene silencing effectively decreased the cytotoxic effect of GMI, suggesting that GMI induces autophagic cell death in H1975/TR cells. This study is the first to reveal the novel role of GMI in inducing cytotoxic effects in H1975 cells and H1975/TR cells with osimertinib resistance through two different forms of cell death: apoptosis and autophagy, respectively.

Subsequently, the patient started gefitinib treatment, and 3 months later, the treatment effect assessment showed a partial response (PR) at regular follow-up according to RECIST evaluation criteria...Two months later, imaging examination showed that the lesions in various parts of the body were stable. Except for dryness of oral and nasal mucosa, the patient did not experience other serious adverse reactions.