EGFR (Epidermal growth factor receptor)

P3, N=339, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Mar 2026 | Trial primary completion date: Dec 2025 --> Mar 2026

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

P3, N=1200, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting

Notably, immune-checkpoint degradation therapy with APCTAC achieves comparable or superior antitumor efficacy while causing significantly less inflammatory damage than antibody therapy. This peptide-based LYTAC system offers a safer, minimally invasive strategy for cancer immunotherapy by combining immune-checkpoint degradation with immunomodulation, laying the groundwork for the development of peptide-based LYTAC as an effective cancer therapy.

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.

These values reflect a potency at least fourfold greater than that of the reference drug Doxorubicin (IC₅₀ = 33 µM)...Conversely, compound 7b, with an IC₅₀ value of 85 µM against MCF-7 cells, was the least active, underscoring the critical role of the phenyl moiety in antiproliferative activity. Furthermore, a molecular docking study was conducted to investigate the binding interactions of 6a within the active sites of EGFR and HER-2, providing insight into its potential mechanism of action.

PIK3CA mutant-mediated cachexia can be overcome by osimertinib (Osi) treatment in Osi-sensitive GEMM. PIK3CA mutant-driven cachexia is mediated through NF-κB activation and can be dampened by combined aspirin treatment. This work provides insights into PIK3CA mutant biological function and mechanisms behind its clinical impacts, and proposes a potential strategy for clinical management.

P3, N=17, Active, not recruiting, University of Texas Southwestern Medical Center | Trial primary completion date: Jun 2026 --> Jun 2025

EGFRi rechallenge is associated with significantly longer PFS, numerically longer OS, and clinically meaningful ORR as compared with non-EGFRi systemic therapy in mCRC, particularly for ctDNA RAS/RAF wild-type mCRC.

We outline mechanisms of action, clinical efficacy, and limitations of FDA-approved tyrosine kinase inhibitors (TKIs) and emerging agents, with emphasis on resistance pathways, both on-target and bypass-mediated, observed during treatment with drugs such as osimertinib, crizotinib, sotorasib, and entrectinib. The role of next-generation sequencing (NGS), liquid biopsy, and comprehensive biomarker profiling in guiding personalized therapy selection is also discussed, along with strategies for sequential therapy and rational combination approaches.