2. Academic Validation
  3. Genetic modulation of ABCB1: Sunvozertinib reverses ABCB1-mediated multidrug resistance in cancer cells

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

  • Cancer Genet. 2026 Jan:300-301:47-57. doi: 10.1016/j.cancergen.2025.12.001.
Lu-Qi Cao 1,  Yuhao Xie 1,  Xuanyu Chen 1,  Harsh Patel 1,  Luoxi Yuan 2,  John Wurpel 1,  Kunxiang Gong 3,  Zhe-Sheng Chen 4
Affiliations

Affiliations

  • 1 Departments of Pharmaceutical Science, College of Pharmacy and Health Science, St John's University, Queens, NY 11439, USA.
  • 2 Departments of Pharmaceutical Science, College of Pharmacy and Health Science, St John's University, Queens, NY 11439, USA; The Masters School 49 Clinton Avenue Dobbs Ferry, NY 10522, USA.
  • 3 Department of Pathology, First School of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080, China. Electronic address: [email protected].
  • 4 Departments of Pharmaceutical Science, College of Pharmacy and Health Science, St John's University, Queens, NY 11439, USA. Electronic address: [email protected].
PMID: 41380312 DOI: 10.1016/j.cancergen.2025.12.001
Abstract

Sunvozertinib is an oral, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) designed to treat non-small cell lung Cancer (NSCLC) patients with EGFR exon 20 insertion mutations under a phase II clinical trial. In this study, we investigated whether sunvozertinib could antagonize ABCB1, also known as multidrug resistance 1 (MDR1/P-gp). ABCB1 is a gene that encodes an important drug transport protein that pumps various substances, including drugs and toxins, out of cells. Sunvozertinib received a high score in docking analysis, indicating a strong interaction between sunvozertinib and ABCB1. ATPase assay indicated that sunvozertinib stimulated ABCB1 ATPase activity in a concentration-dependent manner. MTT assay shows that sunvozertinib significantly reversed ABCB1-mediated MDR but not ABCC1- and ABCG2-mediated MDR. Mechanistic studies show that sunvozertinib significantly reversed ABCB1-mediated MDR by attenuating the efflux activity of the ABCB1 transporter. Furthermore, treatment with sunvozertinib did not change protein expression or subcellular localization of ABCB1. Altogether, these data demonstrate that sunvozertinib, when combined with Other conventional chemotherapeutic agents, can overcome MDR and improve therapeutic effect.

Keywords

ATP-binding cassette (ABC) transporter; Genetics of ABCB1; Multidrug resistance; Sunvozertinib.

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