Related Experiment Video

Updated: Sep 5, 2025

Visualizing Genetic Variants, Short Targets, and Point Mutations in the Morphological Tissue Context with an RNA In Situ Hybridization Assay
10:57

Visualizing Genetic Variants, Short Targets, and Point Mutations in the Morphological Tissue Context with an RNA In Situ Hybridization Assay

Published on: August 14, 2018

10.8K

Location of EGFR exon 20 insertions matters

Andrés Felipe Cardona1, María González-Cao2, Oscar Arrieta3

  • 1Direction of Research, Science, and Education, Luis Carlos Sarmiento Angulo Cancer Treatment and Research Center (CTIC), Bogotá, Colombia.

Cancer Cell
|July 12, 2022
PubMed

Insights

EGFR exon 20 insertions in non-small cell lung cancer (NSCLC) present a treatment challenge. Researchers found only specific near-loop insertions respond to poziotinib, while inhibiting the spindle assembly checkpoint targets resistant tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Epidermal growth factor receptor (EGFR) exon 20 insertions are a distinct subtype of non-small cell lung cancer (NSCLC).
  • These mutations confer resistance to standard EGFR tyrosine kinase inhibitors, creating a therapeutic dilemma.
  • Identifying effective targeted therapies for this subgroup is crucial.

Purpose of the Study:

  • To investigate the differential response of EGFR exon 20 insertions to poziotinib.
  • To explore therapeutic strategies for poziotinib-resistant EGFR exon 20 insertion mutations.

Main Methods:

  • Analysis of patient-derived cell lines and xenograft models with various EGFR exon 20 insertion mutations.
  • Pharmacological treatment with poziotinib.
  • Assessment of tumor growth inhibition and molecular response.
  • Investigating the role of the spindle assembly checkpoint (SAC) in resistance.

Main Results:

  • Poziotinib efficacy is restricted to EGFR exon 20 insertions located in the near loop region.
  • Tumors with poziotinib-resistant exon 20 insertions exhibit sensitivity to pharmacological inhibition of spindle assembly checkpoint components.
  • Targeting SAC components demonstrates potential for overcoming poziotinib resistance.

Conclusions:

  • The localization of EGFR exon 20 insertions dictates poziotinib response.
  • Spindle assembly checkpoint inhibition offers a promising therapeutic avenue for patients with resistant NSCLC harboring EGFR exon 20 insertions.

More Related Videos

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

8.7K
Detection of Rare Mutations in CtDNA Using Next Generation Sequencing11:11

Detection of Rare Mutations in CtDNA Using Next Generation Sequencing

Published on: August 24, 2017

16.9K

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...
6.6K
Exon Recombination02:32

Exon Recombination

The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
Exon shuffling follows “splice frame rules.” Each exon...
3.7K
Non-LTR Retrotransposons03:18

Non-LTR Retrotransposons

As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
11.8K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.4K