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Mitogens and the Cell Cycle02:38

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Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
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  11. Clinical Activity Of Afatinib In Patients With Advanced Non-small-cell Lung Cancer Harbouring Uncommon Egfr Mutations: A Combined Post-hoc Analysis Of Lux-lung 2, Lux-lung 3, And Lux-lung 6.

Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6.

James C-H Yang1, Lecia V Sequist2, Sarayut Lucien Geater3

  • 1Graduate Institute of Oncology, National Taiwan University and National Taiwan University Hospital, Taiwan.

The Lancet. Oncology
|June 9, 2015

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Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
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Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib

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Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer

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View abstract on PubMed

Summary
This summary is machine-generated.

Afatinib showed activity in non-small cell lung cancer with uncommon EGFR mutations, particularly Gly719Xaa, Leu861Gln, and Ser768Ile. However, efficacy was limited for de-novo Thr790Met and exon 20 insertion mutations.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Non-small cell lung cancer (NSCLC) often harbors EGFR mutations, with common mutations (exon 19 deletions, L858R) responding well to inhibitors.
  • A subset of NSCLC patients (10%) present with uncommon EGFR mutations, for whom treatment sensitivity data is limited.
  • Afatinib, an irreversible EGFR inhibitor, was investigated for its efficacy in advanced NSCLC with uncommon EGFR mutations.

Purpose of the Study:

  • To evaluate the activity of afatinib in patients with advanced NSCLC harboring uncommon EGFR mutations.
  • To compare the efficacy of afatinib across different categories of uncommon EGFR mutations.

Main Methods:

  • Post-hoc analysis of prospectively collected data from phase 2 (LUX-Lung 2) and phase 3 (LUX-Lung 3, LUX-Lung 6) trials.

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Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib

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Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
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  • Intention-to-treat population including EGFR mutation-positive, tyrosine kinase inhibitor-naive patients with advanced NSCLC treated with afatinib.
  • Uncommon mutations categorized into three groups: group 1 (point mutations/duplications in exons 18-21), group 2 (de-novo Thr790Met), and group 3 (exon 20 insertions). Outcomes also assessed for specific mutations: Gly719Xaa, Leu861Gln, and Ser768Ile.

    • Main Results:

    • Of 75 patients with uncommon EGFR mutations, 38 were in group 1, 14 in group 2, and 23 in group 3.
    • Objective response rates were 71.1% in group 1, 14.3% in group 2, and 8.7% in group 3.
    • For specific mutations, response rates were 77.8% for Gly719Xaa, 56.3% for Leu861Gln, and 100% for Ser768Ile. Median progression-free survival varied significantly across groups.

    Conclusions:

    • Afatinib demonstrates activity in NSCLC with specific uncommon EGFR mutations, notably Gly719Xaa, Leu861Gln, and Ser768Ile.
    • Efficacy of afatinib is notably lower in patients with de-novo Thr790Met mutations and exon 20 insertions.
    • Findings support informed clinical decision-making for NSCLC patients with diverse EGFR mutation profiles.