No new IRRs nor toxic deaths were reported. ENCO-PANI appears to be as safe and effective in pts treated for a BRAFm mCRC unable to continue CET and may represent a valid alternative therapeutic option in this setting.

P2, N=43, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Jul 2026 --> Dec 2025 | Trial primary completion date: Jul 2026 --> Dec 2025

Clinically, the Notch ligand JAG1 was upregulated in recurrent high-grade glioma patients treated with the oHSV CAN-3110 and correlated with poor prognosis. Heightened EGFR activation in senescent cells was a mechanism to escape cell death, which created a unique opportunity for cetuximab as a senolytic agent. Combination therapy reduced EGFR signaling and induced macrophage-mediated antibody-dependent cellular cytotoxicity, thereby increasing the anti-tumor therapeutic efficacy of OD-0J1.

P1/2, N=44, Completed, Bristol-Myers Squibb | Terminated --> Completed

P2, N=128, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

P2, N=198, Recruiting, Sun Yat-sen University | Trial completion date: Dec 2027 --> Dec 2028 | Trial primary completion date: Mar 2026 --> Dec 2026

P1, N=14, Recruiting, University of Alabama at Birmingham | Trial completion date: Mar 2026 --> Feb 2028 | Trial primary completion date: Mar 2026 --> Feb 2028

Additionally, we found that the copper ionophore disulfiram (DSF) overcame osimertinib resistance by augmenting YTHDC2 expression. Collectively, our findings elucidate a novel YTHDC2-SLC31A1-cuproptosis axis as a key mechanism underlying EGFR-TKI resistance and propose new therapeutic strategies for its reversal.

Noteworthily, ERB-2 could promote ROS accumulation, mitochondrial dysfunction, cell apoptosis and restore Osimertinib sensitivity in Osimertinib-resistant NSCLC cells, eventually lead to effective reversal of Osimertinib resistance in vivo. Collectively, this study identifies ERB-2 as a potent first-in-class ERβ degrader capable of overcoming Osimertinib resistance in NSCLC, putting forward potential solution for clinical unmet need in NSCLC treatment.

By enabling automated analysis of FRET images, FRET-SAM significantly enhances the efficiency and accuracy of FRET two-hybrid assays, while eliminating subjective bias. The capability of FRET-SAM to resolve drug-target interactions establishes it as a promising tool for drug discovery.

When binding to osimertinib, ASV- and SVD-EGFR still revealed two energy minima on their free energy landscapes, but with considerably less conformational probability distribution at collective variable 2 >1.00 Å. In contrast, mobocertinib eliminated the energy minima at collective variable 2 >1.00 Å while decreasing the K745-E762 salt bridge formation rates.ConclusionsMobocertinib outperforms osimertinib in targeting specific subtypes of EGFR exon 20 insertions, highlighting its ability to restore the inactive state of this protein.

The combination of mebendazole and gefitinib effectively suppresses tumor cell viability and modulates key pathways involved in cancer progression. By targeting cytoskeletal integrity and EGFR signaling, it may disrupt cytokine and tumor-microenvironment interactions, supporting further exploration as a strategy to overcome resistance in lung and breast cancers.