Background: EGFR mutations widely exists in NSCLC patients, which are involved in cancer development.
Objective: The function of EGFR mutations in the resistance to TKI treatments of NSCLC was evaluated to provide theoretical support for the clinical management of NSCLC patients.
Methods: A total of 150 NSCLC patients including 118 patients with EGFR mutation and 32 without, were included in this study. The EGFR mutation status and subtypes were analyzed in recruited patients. The distribution of EGFR mutation subtypes and their association with clinicopathological features were also assessed. The prognostic value of EGFR mutation was evaluated by the overall survival of recruited patients. The function of EGFR mutation was estimated, in vitro, in the TKI resistant NSCLC cells with different subtypes of EGFR mutation.
Results: The exon 19 deletion was the most common subtype of EGFR mutation in the enrolled patients followed by the exon 21 L858R point mutation. The EGFR mutations were closely associated with the differentiation degree and the histological types of NSCLC cases. EGFR mutation was an independent prognostic factor of NSCLC with a close relationship with the overall survival of patients. The exon 20 T790M mutation results in the erlotinib resistance through the PI3K/Akt signaling pathway.
Conclusions: The EGFR mutation is a critical factor in the prognosis and for the resistance to TKI treatment in NSCLC. The exon 20 T790M mutation was involved in the erlotinib resistance through PI3K/Akt signaling pathway.
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http://dx.doi.org/10.3233/CBM-210281 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Laboratory of Precision Medicine and Biopharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Recurrent missense mutations in the human epidermal growth factor receptor 2 (HER2) have been identified across various human cancers. Among these mutations, the active S310F mutation in the HER2 extracellular domain stands out as not only oncogenic but also confers resistance to pertuzumab, an antibody drug widely used in clinical cancer therapy, by impeding its binding. In this study, we have successfully employed computational-aided rational design to undertake directed evolution of pertuzumab, resulting in the creation of an evolved pertuzumab variant named Ptz-SA.
View Article and Find Full Text PDFJ Neurosurg
January 2025
8Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University, Kaohsiung.
Objective: This study focuses on epidermal growth factor receptor-mutated lung adenocarcinoma, known for frequent brain metastasis. It aimed to compare the clinical outcomes and cost-effectiveness of combining Gamma Knife radiosurgery (GKRS) with tyrosine kinase inhibitors (TKIs) (GKRS+TKI group) versus TKIs alone (TKI group) for the treatment of patients with newly diagnosed brain metastasis in this condition.
Methods: Study characteristics of the two groups were matched using inverse probability of treatment weighting (IPTW).
J Cancer Res Ther
December 2024
Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Lung Cancer Institute, Shandong, China.
Osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), has revolutionized one of the standard most efficient treatments for EGFR mutation-positive non-small cell lung cancer (NSCLC). Osimertinib, a third-generation EGFR-TKI, is currently one of most efficient treatments in clinical practice. However, it has a potentially fatal side effect: interstitial lung disease (ILD).
View Article and Find Full Text PDFACS Nano
January 2025
Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, South Korea.
Tumor-derived extracellular vesicle (tEV)-associated RNAs hold promise as diagnostic biomarkers, but their clinical use is hindered by the rarity of tEVs among nontumor EVs. Here, we present EV-CLIP, a highly sensitive droplet-based digital method for profiling EV RNA. EV-CLIP utilizes the fusion of EVs with charged liposomes (CLIPs) in a microfluidic chip.
View Article and Find Full Text PDFCancer Commun (Lond)
January 2025
Department of Respiratory and Critical Care Medicine, Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, P. R. China.
Background: The prognosis for non-small cell lung cancer (NSCLC) patients treated with standard platinum-based chemotherapy was suboptimal, with safety concerns. Following encouraging results from a preliminary phase I study, this phase II trial investigated the efficacy and safety of first-line sintilimab and anlotinib in metastatic NSCLC.
Methods: In this open-label, randomized controlled trial (NCT04124731), metastatic NSCLC without epithelial growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or proto-oncogene tyrosine-protein kinase ROS (ROS1) mutations, and previous treatments for metastatic disease were enrolled.
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