Related Experiment Video

Updated: Nov 9, 2025

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
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Selective targeting of KRAS-driven lung tumorigenesis via unresolved ER stress

Iwao Shimomura1,2, Naoaki Watanabe1, Tomofumi Yamamoto1

  • 1Division of Cellular Signaling, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.

JCI Insight
|April 8, 2021
PubMed

Insights

Researchers identified verteporfin, a YAP1 inhibitor, as a potential treatment for KRAS-mutant lung cancer. This drug reduced cancer cell viability and tumor growth, offering new hope for this difficult-to-treat disease.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • KRAS-mutant lung cancer represents a significant portion of lung cancer cases with poor prognosis.
  • Despite advances, targeting mutated KRAS remains a challenge in lung cancer therapy.

Purpose of the Study:

  • To identify novel therapeutic strategies for KRAS-mutant lung cancer.
  • To investigate the efficacy and mechanism of verteporfin in KRAS-driven lung tumorigenesis.

Main Methods:

  • Small-molecule library screening to identify potential drug candidates.
  • In vitro cell viability assays and in vivo tumor suppression studies.
  • Comparative analysis of verteporfin treatment and YAP1 knockdown using siRNA and whole-transcriptome analysis.

Main Results:

  • Verteporfin significantly reduced cell viability in KRAS-mutant lung cancer cells and suppressed tumor growth in vivo.
  • The cytotoxic effects of verteporfin were partially independent of YAP1 inhibition.
  • Verteporfin treatment induced distinct gene expression profiles and activated the ER stress pathway, leading to apoptosis.

Conclusions:

  • Verteporfin demonstrates therapeutic potential against KRAS-mutant lung cancer.
  • The mechanism involves ER stress and apoptotic cell death, partially independent of YAP1.
  • These findings reveal novel vulnerabilities in KRAS-driven lung cancer.
Keywords:
Cell BiologyDrug screensLung cancerOncogenesOncology

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