Related Experiment Video

Updated: Aug 1, 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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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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A Small Molecule Targeting the Intracellular Tyrosine Kinase Domain of ROR1 (KAN0441571C) Induced Significant

Amineh Ghaderi1, Mohammad-Ali Okhovat1, Jemina Lehto2

  • 1Department of Oncology-Pathology, BioClinicum, Karolinska University Hospital Solna, Karolinska Institutet, 171 64 Stockholm, Sweden.

Pharmaceutics
|April 28, 2023
PubMed

Insights

Receptor tyrosine kinase ROR1 is overexpressed in non-small cell lung cancer (NSCLC). A novel inhibitor, KAN0441571C, effectively reduced NSCLC cell proliferation and induced apoptosis, showing promise for targeted therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Receptor tyrosine kinase ROR1 is crucial in oncogenesis and overexpressed in non-small cell lung cancer (NSCLC).
  • ROR1 expression varies across NSCLC subtypes, being more prevalent in non-squamous carcinomas and linked to p53 status.

Purpose of the Study:

  • To evaluate ROR1 expression in NSCLC patients.
  • To investigate the cytotoxic effects of the small molecule ROR1 inhibitor KAN0441571C in NSCLC cell lines.
  • To explore the potential of combining ROR1 and EGFR inhibitors for NSCLC treatment.

Main Methods:

  • ROR1 expression analysis in 287 NSCLC patients.
  • In vitro assessment of KAN0441571C's effects on ROR1 phosphorylation, apoptosis, proliferation, and migration in NSCLC cell lines.
  • Comparative analysis with erlotinib and combination studies.

Main Results:

  • KAN0441571C effectively dephosphorylated ROR1 and induced apoptosis in ROR1-positive NSCLC cell lines in a dose- and time-dependent manner.
  • KAN0441571C demonstrated superior efficacy to erlotinib and synergized with erlotinib to induce apoptosis.
  • KAN0441571C inhibited NSCLC cell proliferation and migration, involving the non-canonical Wnt pathway.

Conclusions:

  • KAN0441571C is a potent ROR1 inhibitor with significant anti-cancer effects in NSCLC models.
  • Combined inhibition of ROR1 and EGFR represents a promising therapeutic strategy for NSCLC.
Keywords:
KAN0441571CNSCLCROR1TTPerlotinibibrutinibsmall molecules

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