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Genetic modulation of ABCB1: Sunvozertinib reverses ABCB1-mediated multidrug resistance in cancer cells

Lu-Qi Cao1, Yuhao Xie1, Xuanyu Chen1

  • 1Departments of Pharmaceutical Science, College of Pharmacy and Health Science, St John's University, Queens, NY 11439, USA.

Cancer Genetics
|December 11, 2025
PubMed

Insights

Sunvozertinib, an EGFR TKI for NSCLC, was found to reverse multidrug resistance (MDR) mediated by ABCB1 (MDR1/P-gp). This suggests sunvozertinib can enhance chemotherapy effectiveness in resistant cancers.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations presents treatment challenges.
  • Multidrug resistance (MDR) mediated by efflux pumps like ABCB1 (MDR1/P-gp) limits therapeutic efficacy.
  • Sunvozertinib is an investigational EGFR tyrosine kinase inhibitor (TKI).

Purpose of the Study:

  • To investigate sunvozertinib's potential to antagonize ABCB1 (MDR1/P-gp) activity.
  • To determine if sunvozertinib can overcome ABCB1-mediated multidrug resistance.

Main Methods:

  • Docking analysis to predict sunvozertinib-ABCB1 interaction.
  • ATPase assay to measure ABCB1 activity.
  • MTT assay to assess drug resistance reversal.
  • Mechanistic studies on transporter efflux and protein expression.

Main Results:

  • Sunvozertinib showed strong interaction with ABCB1 in docking analysis.
  • Sunvozertinib stimulated ABCB1 ATPase activity concentration-dependently.
  • Sunvozertinib reversed ABCB1-mediated MDR, but not ABCC1- or ABCG2-mediated MDR.
  • Sunvozertinib attenuated ABCB1 efflux activity without altering protein expression.

Conclusions:

  • Sunvozertinib effectively antagonizes ABCB1 (MDR1/P-gp).
  • Sunvozertinib can overcome ABCB1-mediated multidrug resistance in cancer cells.
  • Combination therapy with sunvozertinib may improve outcomes for NSCLC patients with MDR.
Keywords:
ATP-binding cassette (ABC) transporterGenetics of ABCB1Multidrug resistanceSunvozertinib

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