T790m and met

Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has overcome the acquired resistance of first- and second-generation EGFR-TKIs due to the EGFR T790M mutation in non-small cell lung cancer (NSCLC). However, acquired resistance to osimertinib remains a significant clinical challenge. Luteolin, a natural flavonoid from traditional Chinese medicine, has exerted antitumor effects in various tumors. In this study, we investigated whether the natural flavonoid luteolin can enhance the antitumor effects of osimertinib in NSCLC cells...

INTRODUCTION: This study aimed to evaluate the treatment outcomes of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy alone or in combination with locoregional brain therapy for advanced EGFR-mutant non-small cell lung cancer (NSCLC) patients with brain metastases. MATERIAL AND METHODS: A retrospective study involving 72 advanced EGFR-mutant NSCLC patients with brain metastases at the Vietnam National Cancer Hospital were conducted. Patients were divided into 2 groups: EGFR-TKI (erlotinib) monotherapy and EGFR-TKI combined with locoregional therapy (γ knife surgery - GKS or whole-brain radiation therapy)...

BACKGROUND: The genetic profiling of non-small cell lung cancer (NSCLC) has contributed to the discovery of actionable targetable mutations, which have significantly improved outcomes in disease with poor prognosis. Molecular epidemiological data of driver mutations in Indian populations have not been extensively elaborated compared to western and eastern Asian NSCLC populations. This study assessed the prevalence and clinical outcomes of EGFR (epidermal growth factor receptor) mutations among the Indian NSCLC cohort in South India...

BACKGROUND: Central nervous system (CNS) metastases is inevitable for epidermal growth factor receptor ( EGFR )-mutant non-small cell lung cancer (NSCLC). AZD3759 is a novel EGFR-TKI with impressive CNS penetration. METHODS: We initiated a phase 2, multi-center, umbrella trial (CTONG1702, NCT03574402). The eighth arm assessed the efficacy and safety of AZD3759 in untreated EGFR -mutated NSCLC with CNS metastases. The primary objective was the objective response rate (ORR)...

We previously demonstrated that neratinib interacted with pemetrexed to kill non-small cell lung cancer (NSCLC) cells. From developing other drug combinations, we observed that several days following exposure, cells activated survival mechanisms to counteract drug toxicity. The present studies attempted to define mechanisms that evolve to reduce the efficacy of neratinib and pemetrexed. Neratinib and pemetrexed synergized to kill NSCLC cells expressing wild-type RAS proteins, mutant KRAS (G12S; Q61H; G12A and G12C) or mutant NRAS (Q61K) or mutant ERBB1 (L858R; L858R T790M and exon 19 deletion)...

BACKGROUND: The combination of erlotinib, a first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), and ramucirumab, an anti-vascular endothelial growth factor receptor (VEGFR) antibody, is one of the most effective treatments for patients with non-small cell lung cancer (NSCLC) and EGFR mutation. However, little is known about the safety and efficacy of this combination treatment for patients with brain metastases. METHODS: This single arm, prospective, open-label, multicenter, phase II study will recruit 32 NSCLC patients with EGFR mutation (except for T790M mutation) and brain metastases (asymptomatic or mild symptoms)...

BACKGROUND: Aumolertinib (HS-10296), a 3rd-generation epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor (TKI), has been shown to have efficacy in treating tumors harboring EGFR sensitive mutations: EGFR in-frame deletions or insertions within exon 19 deletion (19Del) and the exon 21 L858R mutation and EGFR T790M resistance mutation. Research has shown that tumor protein p53 ( TP53 ) mutations and leptomeningeal metastases (LM) are associated with reduced responsiveness and a poor prognosis in patients with advanced non-small cell lung cancer (NSCLC) who have received targeted therapy with EGFR-TKIs...

Multiple primary malignant neoplasms (MPMNs) are difficult to identify from the metastasis or recurrence of malignant tumors. Additionally, the genetic mutations in each primary tumor vary from each other; therefore, it is critical to explore potential abnormal genes. Next-generation sequencing (NGS) technology has emerged as a reliable approach for detecting mutated genes in primary tumors and can provide several targeted therapeutic options for patients with MPMNs. Here, we report a case of metachronous multiple primary malignant neoplasm (MMPMN) patient with primary ovarian and breast cancer...

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Mobocertinib is an oral tyrosine kinase inhibitor (TKI) that selectively targets epidermal growth factor receptor exon 20 insertion (EGFRex20ins) mutations. It is a structural analog of the third-generation TKI osimertinib, which targets EGFR T790M mutant non-small cell lung cancer (NSCLC); however, mobocertinib gains selectivity for EGFRex20ins mutants over wild type (WT) by interacting with the C790 gatekeeper residue of EGFR. This is accomplished via a carboxylated isopropyl ester moiety at the C5-position of mobocertinib's central pyrimidine core...

INTRODUCTION: Non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation has a higher incidence of brain metastases than wild-type EGFR mutations. Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), targets both EGFR-TKI sensitizing and T790M-resistance mutations and has a higher brain penetration rate relative to first- and second-generation EGFR-TKIs. Therefore, osimertinib has become a preferred first-line therapy for advanced EGFR mutation-positive NSCLC...

The T790M mutation in the epidermal growth factor receptor gene causes most acquired resistance to firstor second-line epidermal growth factor receptor-tyrosine kinase inhibitors in advanced non-small-cell lung cancer. The results of T790M testing can guide subsequent treatment. Despite the availability of guidelines from international organisations, T790M testing practices in Hong Kong must be streamlined and adapted to the Hospital Authority setting. To address this issue, a panel of experts in oncology and pathology met for discussion of key topics regarding T790M testing practices in Hong Kong, including the appropriate timing of testing and re-testing, as well as optimal testing methods...

BACKGROUND: Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has limited treatment options for patients with EGFR-mutated non-small-cell lung cancer (NSCLC). Although osimertinib or afatinib alone induced drug-resistant clones with EGFR secondary mutation in a preclinical model, its combination prevented the appearance of these mutations. We investigated alternating-dose therapy of osimertinib and afatinib in patients with EGFR-mutant NSCLC in a single-arm Phase II trial...

INTRODUCTION: The abnormal expression and mutagenesis of EGFR drives both the development and progression of a multitude of human cancers. Further mutations within the tyrosine kinase region of the EGFR subsequently contribute to resistance to targeted drugs. What is not known is how these mutations affect progression-related behaviors of cancer cells. METHODS: The mutagenesis of EGFR T790M, L858R, and T790M/L858R was performed via oligo primer-guided polymerase chain reaction (PCR)...

AIM: The present study is to investigate the association between T790M status and clinical characteristics of patients with EGFR-sensitive advanced non-small cell lung cancer (NSCLC) who progressed the initial epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) administration. METHODS: A total of 167 patients with EGFR-sensitive mutations advanced NSCLC who had successful genetic tests and progressed the initial EGFR-TKI treatment were included in this study retrospectively...

BACKGROUND: Bladder metastasis from lung cancer with epidermal growth factor receptor (EGFR) mutation is extremely rare. Here, we report a case of bladder metastasis from lung adenocarcinoma with EGFR mutation. CASE SUMMARY: A 53-year-old female patient was diagnosed with advanced lung adenocarcinoma with EGFR exon 19 deletion. Multiple nodules on the bladder wall were found by regular examination of the pelvic cavity through computed tomography during targeted therapy...

BACKGROUND: The epidermal growth factor receptor (EGFR) p.Thr790Met (T790M) mutation was discovered as a resistance mechanism in patients with lung cancer treated with first- and second-generation tyrosine kinase inhibitors. Further studies revealed the EGFR T790M mutation in treatment-naive non-small cell lung carcinoma (NSCLC) and as a rare germline mutation strongly associated with NSCLC. Somatic EGFR T790M mutations have been reported in a limited population of patients with triple-negative breast cancer...

EGFR (epidermal growth factor receptor), a surface protein on the cell, belongs to the tyrosine kinase family, responsible for cell growth and proliferation. Overexpression or mutation in the EGFR gene leads to various types of cancer, i.e., non-small cell lung cancer, breast, and pancreatic cancer. Bioactive molecules identified in this genre were also an essential source of encouragement for researchers who accomplished the design and synthesis of novel compounds with anticancer properties. World Health Organization (WHO) report states that antibiotic resistance is one of the most severe risks to global well-being, food safety, and development...

Right upper lobectomy and lymph node dissection was performed on an 85-year-old male clinically diagnosed with primary lung cancer at the age of 78 years. His post-operative pathologic staging was adenocarcinoma pT1aN0M0, StageⅠ A1, and he was positive for the epidermal growth factor receptor(EGFR). Two years post-operation, a PET scan revealed cancer recurrence due to mediastinal lymph node metastasis. The patient received mediastinal radiation therapy followed by cytotoxic chemotherapy. Nine months later, a PET scan revealed bilateral intrapulmonary metastases and metastases to the ribs...

Introduction: Up to 50% of non-small cell lung cancer (NSCLC) harbor EGFR alterations, the most common etiology behind brain metastases (BMs). First-generation EGFR-directed tyrosine kinase inhibitors (EGFR-TKI) are limited by blood-brain barrier penetration and T790M tumor mutations, wherein third-generation EGFR-TKIs, like Osimertinib, have shown greater activity. However, their efficacy has not been well-studied in later therapy lines in NSCLC patients with BMs (NSCLC-BM). We sought to compare outcomes of NSCLC-BM treated with either first- or third-generation EGFR-TKIs in first-line and 2nd-to-5th-line settings...