Related Experiment Video

Updated: May 8, 2026

Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
07:29

Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment

Published on: April 22, 2019

Cetuximab attenuates its cytotoxic and radiosensitizing potential by inducing fibronectin biosynthesis

Iris Eke1, Katja Storch, Mechthild Krause

  • 1Authors' Affiliations: OncoRay-National Center for Radiation Research in Oncology; Department of Radiation Oncology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden; German Cancer Consortium (DKTK); German Cancer Research Center (DKFZ); and Institute of Radiooncology, Helmholtz Center Dresden-Rossendorf, Dresden, Germany.

Cancer Research
|August 17, 2013
PubMed

Insights

Cell adhesion to fibronectin can cause resistance to lung cancer drug cetuximab. This interaction boosts fibronectin production, creating a self-defeating resistance mechanism against the targeted therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Acquired resistance to targeted therapies is a significant clinical challenge.
  • Epidermal Growth Factor Receptor (EGFR) inhibitors, like cetuximab, are widely used for lung cancer treatment.
  • Cancer cell-substrate interactions influence therapeutic sensitivity.

Purpose of the Study:

  • To investigate the impact of cell-fibronectin interactions on cetuximab efficacy in non-small cell lung cancer (NSCLC).
  • To elucidate the mechanisms by which cell adhesion affects EGFR-targeted therapy response.

Main Methods:

  • In vitro and in vivo studies using human NSCLC cells.
  • Assessing the effects of cell adhesion to fibronectin on radioresistance and cetuximab sensitivity.
  • Analyzing fibronectin biosynthesis induction by cetuximab.
  • Investigating the role of the p38-MAPK-ATF2 signaling pathway.
  • Utilizing RNA interference (RNAi) to inhibit fibronectin expression.

Main Results:

  • Cell adhesion to fibronectin promoted radioresistance in NSCLC cells.
  • Fibronectin interactions attenuated the cytotoxic and radiosensitizing effects of cetuximab.
  • Cetuximab treatment induced significant fibronectin biosynthesis.
  • This induction was mediated by the p38-MAPK-ATF2 pathway.
  • Inhibiting fibronectin with RNAi enhanced cetuximab's efficacy.

Conclusions:

  • Cell adhesion to fibronectin blunts the effectiveness of cetuximab in lung cancer.
  • Cetuximab treatment induces fibronectin production, creating a self-attenuating resistance mechanism.
  • Targeting cell-fibronectin interactions or fibronectin biosynthesis may overcome cetuximab resistance.

More Related Videos

High-Content Screening Assay for the Identification of Antibody-Dependent Cellular Cytotoxicity Modifying Compounds13:59

High-Content Screening Assay for the Identification of Antibody-Dependent Cellular Cytotoxicity Modifying Compounds

Published on: August 18, 2023

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...
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 specific...
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...
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.