Initial studies were done by molecular docking of five analogs of quinazoline- quinazolinone hybrids, erlotinib, and doxorubicin against the epidermal growth factor receptor. The insertion of a nitro group at the 7 position of quinazolinone enhanced the cytotoxic efficacy against MCF-7 cells, likely attributable to electronic influences. Consequently, this compound could serve as a lead compound in the search for new classes of effective anticancer agents.

Osimertinib dose reduction in the first-line setting was not associated with inferior OS, suggesting that appropriate dose modification helps maintain PS. Transition to BSC after progression, rather than initial dose intensity, was associated with poor prognosis.

This report of a patient with the rare p.(Cys797Ala) EGFR acquired mutation highlights the role of molecular modelling and IHC for phosphorylated proteins as tools to functionally characterize variants of unknown significance and help clinical decisions.

Patients with EGFR-mutant LUSC or LUAS had shorter overall survival on first-line osimertinib compared with those with EGFR-mutant LUAD...Combined EGFR and MET inhibition suppressed tumor growth in patient-derived xenograft models of LUSC transformation. Together, these findings highlight Rb pathway inactivation as a promoter of LUSC transformation in EGFR-mutant lung cancer and identify MET signaling as a therapeutic vulnerability that may suppress plasticity in this setting and extend response to targeted therapy.

Furthermore, we introduce a positive correlation between compound selectivity for IMPDH2 and the ability to synergize with Osimertinib: the standard of care for EGFR-mutant non-small cell lung cancer. Overall, our results suggest that specifically blocking IMPDH2 is an effective therapeutic strategy for BM by overcoming the immune suppressive effects that have hindered the clinical development of pan-IMPDH inhibitors in the past. An IMPDH2 specific therapy could be coadministered with primary tumor standard of care treatments to provide a safe and interceptional approach for BM.

For OS, both cetuximab + chemotherapy [hazard ratio (HR)=0.853; 95% CI: 0.775-0.938; P=0.001] and panitumumab + chemotherapy (HR=0.855; 95% CI: 0.738-0.992; P=0.038) exhibited statistically significant superiority compared with bevacizumab + chemotherapy...In the present sensitivity analysis, UDP glucuronosyltransferase family 1 member A1-guided bevacizumab + 5-fluorouracil, leucovorin and irinotecan demonstrated favorable outcomes, with OS and PFS P-scores of 0.932 and 0.992, respectively; however, these findings were derived from a single trial with limited comparability...Treatment benefit from anti-EGFR therapy was markedly influenced by primary tumor location, with notable benefit observed in left-sided tumors and no benefit in right-sided tumors. These findings support tumor sidedness-guided treatment selection in clinical practice, favoring anti-EGFR-based therapy for left-sided and bevacizumab-based therapy for right-sided RAS wild-type mCRC.

Notably, artificial catalysts lacking spatial confinement exhibit higher defluorination efficiency. This work reveals that biological spatial confinement reshapes reaction pathways and modulates activation barriers, thereby deepening the mechanistic understanding of fluorinated drug metabolism and supporting rational design for safer pharmaceuticals and environmentally benign detoxification strategies.

Small interfering RNA (siRNA)-mediated knockdown of DAAM1 enhances sensitivity to osimertinib, providing functional support for this causal prediction. Overall, CauFinder enables actionable target nomination and testable hypotheses for intervening in disease-relevant state transitions using observational transcriptomic data.

hrFP-E is equipped with a nitroreductase (NTR)-sensitive motif activated in hypoxic regions to release a FAK degrader (FP) and an EGFR inhibitor (Erlotinib)...This platform is inherently modular and compatible with alternative oncogenic drivers and disease-specific gates. Our work establishes mechano-chemical therapeutics, spatiotemporally controlled degraders that rewire tumor mechanics alongside growth signaling, as a generalizable strategy for solid tumor treatment.

Our findings not only reveal a clinically relevant resistance mechanism to KRAS G12D inhibition but also provide a rational, effective combined strategy. Ultimately, the combination of HRS-4642 with nimotuzumab offers a promising therapeutic strategy for PDAC patients harboring KRAS G12D mutations, laying a foundation for advancing clinical research in overcoming resistance to KRAS G12D-targeted therapies.

P1, N=120, Not yet recruiting, Shanghai EpimAb Biotherapeutics Co., Ltd.