erlotinib

P1, N=55, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

Compounds 20c and 21c exhibited potent inhibition of EGFR, with IC50 values of 71 and 64 nM, respectively, surpassing the reference erlotinib (IC50 = 80 nM). Moreover, compounds 20c and 21c exhibited BRAFV600E inhibitory action with IC50 values of 49 and 41 nM, respectively, which are somewhat less potent than the reference drug Vemurafenib...Compounds 20c and 21c showed a notable decrease in TNF-α and IL-6 levels compared with dexamethasone, suggesting an immunomodulatory effect. Molecular docking further validated the favorable orientation of 20c and 21c within the ATP-binding pocket of EGFR and BRAFV600E. These findings underscore compounds 20c and 21c as innovative dual-target scaffolds with significant promise for anticancer drug development.

The IC₅₀ values for compounds NAP-SePh and NAP-Se(n-Oct) were 27.92 ± 3 µM and 23.06 ± 3 μM, respectively. Molecular docking simulations revealed that NAP-SePh and NAP-Se(n-Oct) show binding affinities of -10.39 and -8.53 kcal/mol for the (1M17) active, and -10.66 and -10.59 kcal/mol for the (4HJO) inactive conformation of the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) in which erlotinib, a well-known anticancer drug, binds.

In conclusion, BKDRP presents a novel biological knowledge-driven deep neural network model for cancer drug response prediction that shows strong predictive accuracy and interpretability. By integrating multi-omics data and incorporating domain knowledge, BKDRP has the strong potential for applications in biomarker discovery and the advancement of personalized oncology.

Notably, compound 3d exhibited in vivo antitumor activity while demonstrating minimal toxicity to normal tissues. These findings collectively suggest that 3d represents a promising candidate for further development as a potential therapeutic agent for hepatocellular carcinoma treatment.

Commonly used GSIs include DAPT and RO4929097, which enhance the efficacy of agents, such as gemcitabine (PDAC), paclitaxel, osimertinib, erlotinib, and crizotinib (NSCLC), and 5-FU (gastric cancer, TNBC)...Additional research directions include addressing the tumor microenvironment and EMT-driven resistance, elucidating the mechanisms of immune evasion, and inhibiting tumor angiogenesis. Finally, leveraging artificial intelligence and big-data-driven personalized medicine, including sex-specific considerations, will be essential for improving patient outcomes.

P3, N=311, Completed, Guangdong Association of Clinical Trials | Unknown status --> Completed

Drug sensitivity analysis further suggested that Lapatinib and Erlotinib may be beneficial in HNSC patients with high PRKAR1B expression. Lastly, PRKAR1B protein expression was upregulated in clinical HNSC samples. Overall, this study thoroughly examined PRKAR1B expression and its prognostic significance in HNSC, investigated related molecular pathways and immune cell interactions, and validated its role via in vitro experiments.

In silico molecular docking studies revealed strong and stable interactions of the synthesized compounds with the ATP-binding pocket of the EGFR kinase domain, comparable to that of the reference drug, erlotinib...In silico Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis predicted favorable pharmacokinetic and safety profiles for the lead compounds.Collectively, the results suggest that fused isoxazole and fused 1,2,3-triazole derivatives, especially compounds 4 h, 5d and 5 h, represent promising lead molecules for the development of novel EGFR-targeted therapies for lung cancer. Further in vivo studies and detailed pharmacological investigations are warranted to validate their therapeutic potential.

Among these, JS04 emerged as the most potent derivative, exhibiting antiproliferative activity with IC₅₀ values of 8.11 ± 0.43 μM and 11.58 ± 1.68 μM against H1975 (EGFR-TKI resistant) and A549 (EGFR-independent) cell lines, respectively, outperforming gefitinib. Real-time impedance (xCELLigence) and flow cytometry analyses demonstrated that JS04 induced rapid, dose-dependent apoptosis, achieving 74% apoptotic cell death at 20 μM, substantially higher than erlotinib (13%). Proteome profiling confirmed activation of both intrinsic (downregulation of Bcl-2, Bcl-xL, and survivin) and extrinsic (upregulation of TRAIL R2/D5) apoptotic pathways, accompanied by G₂/M phase cell cycle arrest comparable to osimertinib...Computational studies, molecular docking and 100 ns molecular dynamics simulations indicated that JS04 forms stable hydrogen bonds with hinge region residues MET793 and GLN791, and exhibits strong binding affinity toward the EGFRL858R/T790M kinase. Collectively, these findings position JS04 as a promising quinazoline-based lead candidate that effectively triggers dual apoptotic mechanisms, selectivity toward H1975 cells, and demonstrates early indications of safety, warranting further biochemical validation, structure-activity optimisation, and in vivo efficacy evaluation.

She subsequently received bevacizumab and erlotinib and achieved a favorable response. This case illustrates the practical challenges faced in treating fumarate hydratase-deficient renal cell carcinoma, including the lack of established systemic treatment guidelines and management of treatment-related adverse events. It highlights the value of integrating radiotherapy during interruptions in systemic therapy and the importance of multidisciplinary collaboration in this rare tumor.

Drug sensitivity predictions suggested that patients with this cell subtype may respond better to specific anticancer agents (e.g., AZD3759, Erlotinib, Gefitinib). Moreover, their predictive value in CRC therapy was revealed. The study provided new perspectives for CRC prognosis evaluation and personalized immune-targeted combination therapies.