Related Experiment Video

Updated: Apr 14, 2026

A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds
13:34

A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds

Published on: April 6, 2016

10.8K

Genetic and pharmacologic inhibition of EPHA2 promotes apoptosis in NSCLC

Katherine R Amato, Shan Wang, Andrew K Hastings

    The Journal of Clinical Investigation
    |April 10, 2014
    PubMed

    Insights

    Targeting the EPHA2 receptor tyrosine kinase (RTK) inhibits non-small cell lung cancer (NSCLC) growth. This study shows EPHA2 is crucial for NSCLC progression and that the inhibitor ALW-II-41-27 effectively reduces tumor growth in preclinical models.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Cancer Research

    Background:

    • EPHA2 receptor tyrosine kinase (RTK) is overexpressed in non-small cell lung cancers (NSCLCs).
    • EPHA2 overexpression correlates with poor clinical outcomes in NSCLC patients.
    • EPHA2 represents a potential therapeutic target for NSCLC treatment.

    Purpose of the Study:

    • To investigate the role of EPHA2 in NSCLC progression.
    • To evaluate the therapeutic potential of targeting EPHA2 in NSCLC.

    Main Methods:

    • Targeted disruption of EPHA2 in a murine model of Kras-mutant NSCLC.
    • EPHA2 knockdown in human NSCLC cell lines.
    • Assessment of apoptosis and cell viability.
    • Treatment with an EPHA2 RTK inhibitor (ALW-II-41-27) in vitro and in vivo NSCLC xenograft models.

    Main Results:

    • Targeted disruption of EPHA2 impaired tumor growth in a murine NSCLC model.
    • EPHA2 knockdown reduced NSCLC cell growth and viability, confirming its epithelial cell-autonomous role.
    • Targeting EPHA2 induced apoptosis by decreasing BAD phosphorylation.
    • The EPHA2 inhibitor ALW-II-41-27 demonstrated time- and dose-dependent inhibition of NSCLC cell viability in vitro.
    • ALW-II-41-27 induced tumor regression in human NSCLC xenografts in vivo.

    Conclusions:

    • EPHA2 plays a critical role in the maintenance and progression of NSCLCs.
    • Targeting EPHA2, particularly with inhibitors like ALW-II-41-27, shows significant promise for NSCLC therapy.
    • ALW-II-41-27 effectively inhibits EPHA2-mediated tumor growth in preclinical NSCLC models.

    More Related Videos

    Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure09:38

    Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

    Published on: August 11, 2017

    9.3K
    Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids08:52

    Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

    Published on: November 22, 2021

    4.8K

    Related Concept Videos

    Mitogens and the Cell Cycle02:38

    Mitogens and the Cell Cycle

    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...
    8.5K
    Targeted Cancer Therapies02:57

    Targeted Cancer Therapies

    The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
    There are several types of targeted therapies against...
    9.2K
    The Extrinsic Apoptotic Pathway01:17

    The Extrinsic Apoptotic Pathway

    The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
    9.4K
    The Intrinsic Apoptotic Pathway01:31

    The Intrinsic Apoptotic Pathway

    Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
    9.3K
    Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

    Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

    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...
    70
    Pharmacogenomics: Identification of New Drug Targets01:29

    Pharmacogenomics: Identification of New Drug Targets

    Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
    94