Related Experiment Video

Updated: Feb 9, 2026

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

8.0K

ERBB Signaling Interrupted: Targeting Ligand-Induced Pathway Activation

Frederick H Wilson1,2,3, Katerina Politi1,3,4

  • 1Department of Medicine, Section of Medical Oncology, Yale School of Medicine, New Haven, Connecticut. katerina.politi@yale.edu frederick.wilson@yale.edu.

Cancer Discovery
|June 3, 2018
PubMed

Insights

A patient with a specific gene rearrangement (CD74-NRG1) in lung cancer responded exceptionally well to an experimental ERBB3 antibody. This finding highlights NRG1 rearrangements as potential targets for cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Lung adenocarcinoma can harbor specific gene rearrangements.
  • CD74-NRG1 rearrangements activate ERBB2-ERBB3 signaling pathways.
  • NRG1 rearrangements are found in various solid tumors at low frequencies.

Purpose of the Study:

  • To investigate the therapeutic potential of targeting ERBB3 in patients with CD74-NRG1 rearrangements.
  • To assess the clinical response to an anti-ERBB3 antibody in a patient with advanced lung adenocarcinoma and this specific gene rearrangement.

Main Methods:

  • Case study of a patient with advanced lung adenocarcinoma.
  • Analysis of tumor genomics for gene rearrangements.
  • Administration of an experimental anti-ERBB3 antibody therapy.
  • Evaluation of therapeutic response.

Main Results:

  • The patient exhibited an exceptional therapeutic response to the anti-ERBB3 antibody.
  • The CD74-NRG1 rearrangement was identified as the underlying molecular driver.
  • This specific rearrangement promotes ERBB2-ERBB3 heterodimerization and downstream signaling activation.

Conclusions:

  • Targeting ERBB3 is a viable therapeutic strategy for cancers with CD74-NRG1 rearrangements.
  • NRG1 rearrangements represent actionable targets across various solid tumors.
  • Personalized medicine approaches can yield significant clinical benefits for patients with rare genetic alterations.

More Related Videos

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor07:16

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor

Published on: September 13, 2018

20.7K
Task Interruption and Resumption Paradigm for Testing the Activation and Pursuit of an Abstract Thinking Goal06:45

Task Interruption and Resumption Paradigm for Testing the Activation and Pursuit of an Abstract Thinking Goal

Published on: April 18, 2017

6.6K

Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.6K
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
10.1K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.4K
What is Cell Signaling?02:03

What is Cell Signaling?

Despite the protective membrane that separates a cell from the environment, cells need the ability to detect and respond to environmental changes. Additionally, cells often need to communicate with one another. Unicellular and multicellular organisms use a variety of cell signaling mechanisms to communicate to respond to the environment.
131.0K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
8.5K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
10.7K