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Updated: Feb 5, 2026

Enrichment for Chemoresistant Ovarian Cancer Stem Cells from Human Cell Lines
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Mapping CSC-Mediated Ovarian Cancer Chemoresistance via CXCR4-PET to Guide Precision Cisplatin Re-Sensitization

Lixia Feng1,2,3,4, Simei Zhao1, Zheng Wei5

  • 1Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|February 3, 2026
PubMed

Insights

Targeting CXC motif chemokine receptor 4 (CXCR4) in ovarian cancer stem cells (CSCs) shows promise. CXCR4 blockade and imaging can improve chemoresistance treatment and reduce relapse risks in ovarian cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Medical Imaging

Background:

  • Targeting cancer stem cells (CSCs) is crucial for overcoming chemoresistance and relapse in ovarian cancer (OC).
  • Identifying targetable markers for ovarian CSCs remains a significant challenge in OC research.
  • CXC motif chemokine receptor 4 (CXCR4) is investigated as a potential functional marker for ovarian CSCs.

Purpose of the Study:

  • To evaluate CXCR4 as a targetable marker for ovarian CSCs.
  • To develop a translational model for CXCR4-targeted imaging and therapy in OC.
  • To assess the efficacy of CXCR4 blockade in combination with chemotherapy.

Main Methods:

  • Analysis of CXCR4 expression in chemoresistant ovarian CSC-like cells.
  • In vitro and in vivo assessment of self-renewal capacity and chemoresistance.
  • Administration of CXCR4 inhibitor AMD3100 and cisplatin (CDDP).
  • Positron emission tomography (PET) imaging using CXCR4-targeted [68Ga]Ga-Pentixafor.

Main Results:

  • CXCR4 was identified as a potential stemness marker in ovarian CSCs, correlating with self-renewal and chemoresistance.
  • AMD3100 impaired CSC self-renewal and enhanced cisplatin sensitivity.
  • [68Ga]Ga-Pentixafor PET imaging accurately delineated CXCR4-high tumors in xenografts and patient-derived models.
  • Combination therapy of AMD3100 and CDDP showed significant antitumor effects in CXCR4-high tumors but not in CXCR4-low tumors.

Conclusions:

  • CXCR4 represents a functional CSC marker associated with chemoresistance in ovarian cancer.
  • CXCR4-targeted PET imaging can guide the selection of patients for AMD3100 therapy.
  • This approach holds potential for clinical translation in managing ovarian cancer.
Keywords:
CXC motif chemokine receptor 4cancer stem cellschemoresistanceovarian cancerpositron emission tomography/computed tomography

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