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CX Chemokine Receptor 7 Contributes to Survival of KRAS-Mutant Non-Small Cell Lung Cancer upon Loss of Epidermal

Bin Liu1, Shanshan Song2,3, Rita Setroikromo4

  • 1Groningen Research Institute of Pharmacy, Department of Chemical and Pharmaceutical Biology, University of Groningen, 9713 AV Groningen, The Netherlands. bin.liu@rug.nl.

Cancers
|April 3, 2019
PubMed

Insights

Targeting epidermal growth factor receptor (EGFR) suppressed KRAS-driven lung cancer growth. Dual inhibition of EGFR and CX chemokine receptor 7 (CXCR7) offers a promising therapeutic strategy for non-small cell lung cancer (NSCLC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • KRAS-driven non-small cell lung cancer (NSCLC) lacks effective targeted treatments.
  • Epidermal growth factor receptor (EGFR) is a potential therapeutic target in NSCLC.

Purpose of the Study:

  • To investigate targeting EGFR as a therapeutic strategy in KRAS-driven lung cancer.
  • To explore the interaction between EGFR and CX chemokine receptor 7 (CXCR7) in NSCLC.

Main Methods:

  • Utilized CRISPR/Cas9 to generate EGFR knockout NSCLC cell lines.
  • Assessed tumor growth suppression, CXCR7 expression, and MAPK pathway activation (ERK1/2).
  • Investigated the effects of dual EGFR and CXCR7 inhibition.
  • Analyzed CXCR7 protein expression in NSCLC patient samples.

Main Results:

  • EGFR ablation suppressed tumor growth and increased CXCR7 expression and MAPK activation in KRAS-dependent cells.
  • Dual EGFR and CXCR7 inhibition synergistically reduced cell growth and MAPK activation.
  • CXCR7 expression showed genotype dependency and was detected in all NSCLC patient samples, with higher levels in adenocarcinoma.

Conclusions:

  • EGFR and CXCR7 exhibit a critical interaction in NSCLC.
  • Combined EGFR and CXCR7 inhibition represents a potential therapeutic approach for NSCLC patients.
Keywords:
CXCR7KRASepidermal growth factor receptor (EGFR)gene editinglung cancertargeted therapy

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