Related Experiment Video

Updated: Jan 15, 2026

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
08:52

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

Published on: November 22, 2021

4.5K

ACTN4 Gene Amplification and Actinin-4 Protein Expression for Osimertinib Efficacy in EGFR-Mutant NSCLC

Takehiro Tozuka1, Rintaro Noro1, Yutaka Naito2

  • 1Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.

Cancer Science
|October 11, 2025
PubMed

Insights

Actinin-4 protein expression and gene amplification are linked to poorer outcomes for patients with epidermal growth factor receptor-mutant non-small cell lung cancer treated with osimertinib. These findings identify potential biomarkers for predicting treatment response.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Actinin-4 (ACTN4) is an actin-bundling protein associated with cancer progression.
  • Osimertinib is a targeted therapy for epidermal growth factor receptor-mutant non-small cell lung cancer (NSCLC).
  • The prognostic role of ACTN4 in NSCLC treated with osimertinib remains unclear.

Purpose of the Study:

  • To investigate the association between ACTN4 amplification, actinin-4 protein expression, and osimertinib efficacy in EGFR-mutant NSCLC.
  • To identify potential biomarkers for predicting treatment response to first-line osimertinib therapy.

Main Methods:

  • Retrospective analysis of 63 patients with EGFR-mutant NSCLC receiving first-line osimertinib.
  • Immunohistochemistry (IHC) for actinin-4 protein expression on pretreatment tumor tissues.
  • Fluorescence in situ hybridization (FISH) to assess ACTN4 amplification in IHC-positive cases.

Main Results:

  • Actinin-4 IHC positivity was observed in 33 out of 63 patients.
  • Actinin-4 IHC-positive patients had significantly shorter progression-free survival (PFS) and overall survival (OS) compared to negative cases.
  • FISH revealed ACTN4 amplification in 4 of the 33 IHC-positive cases, with numerically shorter PFS and OS observed in these patients.

Conclusions:

  • ACTN4 amplification and elevated actinin-4 protein expression are associated with poor osimertinib efficacy in EGFR-mutant NSCLC.
  • ACTN4 status may serve as a prognostic biomarker for osimertinib treatment outcomes.
  • Further research is warranted to validate these findings and explore therapeutic strategies targeting ACTN4.
Keywords:
ACTN4EGFRactinin‐4non‐small cell lung cancerosimertinib

More Related Videos

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib09:38

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

Published on: June 26, 2019

8.4K
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

7.8K

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.6K
Actin Polymerization and Cell Motility01:13

Actin Polymerization and Cell Motility

Actin is a family of globular proteins that are highly abundant in eukaryotic cells. It makes up approximately 1-5% of total cell protein concentration. Actin monomers polymerize to form a complex network of polarized filaments, the actin cytoskeleton, that plays a crucial role in many cellular processes, including cell motility, division, endocytosis, and metastasis of cancer cells.
Actin cytoskeleton dynamics can produce pushing, pulling, and resistance forces that help the cell to migrate....
6.5K
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...
7.7K