EGFR (Epidermal growth factor receptor)

P3, N=390, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2026 --> Feb 2027 | Trial primary completion date: Oct 2026 --> Dec 2025

P2, N=278, Recruiting, AstraZeneca | Trial primary completion date: Mar 2027 --> Apr 2029

Real-world evidence confirms the long-term effectiveness and safety of pembrolizumab monotherapy for advanced NSCLC with PD-L1 ≥50%. Survival outcomes closely mirrored those from previous trials, supporting the generalizability of pembrolizumab's benefit across routine practice.

Multiplex immunofluorescence staining demonstrated that BCL-xL inhibition effectively triggered apoptosis in heterogeneous PDX tumor slice models, including models harboring oncogenic BRAF mutations. Our findings suggest that cetuximab-resistant CRC retains apoptotic competence, and that BCL-xL inhibition serves as a robust alternative therapeutic strategy that is largely independent of the tumor mutational profile.

P1/2, N=144, Recruiting, Engeneic Pty Limited | Not yet recruiting --> Recruiting

The initial HTVS (high-throughput virtual screening), followed by XP analysis and molecular mechanics (MMGBSA) and ADME profiling, led to the identification of Cycloguanil (antimalarial) and Metformin (antidiabetic) as the putative lead molecules with the potential to inhibit the EGFR...Cycloguanil inhibited the EGFR with a half maximal inhibitory concentration (IC50) of IC50 of 490 nM compared to erlotinib with an IC50 of 222 nM...From the analysis, it was deduced that cycloguanil exhibited the most potent cytotoxicity towards the A549 cell with an IC50 of 6.83 μM, followed by HCT-116 with an IC50 of 9.32 μM, while in MCF-7, it exhibited an IC50 of 14.82 μM. The lead molecule, cycloguanil, may plausibly serve as an important template that may be optimized by performing bioisosteric replacements, leading to a putative kinase inhibitor with a potent anticancer profile.

Importantly, we identify resistance mechanisms specific to protein degraders: E3 ligase loss or mutation, EGFR alterations that disrupt ternary complex formation, deubiquitinase upregulation, and degradation pathway dysfunction. By integrating structural biology, medicinal chemistry, and clinical insights, this review provides a comprehensive roadmap for developing next-generation EGFR degraders capable of overcoming resistance and improving outcomes for lung cancer patients.

Ectopic expressions of DNMT1 impose an epigenetic checkpoint at those target loci by methylation of promoter DNA of the respective genes. We conclude that, gene specific hypomethylation of some genes, including COL1A1, COL1A2, COL4A1, SPP1, SPARC, and THBS2 drives COAD and would serve as potential markers for COAD screening.

EGFR mutation discordance is common and clinically relevant, particularly in NSCLC, but varies substantially by sampling strategy, biofluid, treatment context, and metastatic site. Given the high between-study heterogeneity and the predominance of NSCLC and Asian cohorts, pooled estimates should be interpreted as descriptive summaries rather than universally generalisable benchmarks. These findings support integrated and context-aware sampling strategies for EGFR-targeted therapy and resistance monitoring.

TP53 and EGFR gene mutations were associated with more aggressive cancer phenotypes, leading to a 2.6-fold increase in the risk of death.

Clinical staff should prioritize attention to the physical and psychological distress experienced by patients with cancer with EGFRI-induced skin toxicities. Implementing enhanced symptom evaluation and management, providing tailored psychological support, and offering professional guidance can help patients effectively cope with their symptoms and foster their self-growth.