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Mechanisms and Therapeutic Strategies for Minority Cell-Induced Paclitaxel Resistance and Tumor Progression Mediated

Xueyan Feng1,2, Di Zhang1,2,3, Guoxun Wang3

  • 1State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry, CAS Research/Education Center for Excellence in Molecular Sciences, Chinese Academy of Science, Beijing, 100190, P. R. China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|April 24, 2025
PubMed

Insights

Minority-resistant cancer cells enhance tumor drug resistance and progression through mechanical force transmission, a process called mechano-assimilation. Disrupting this mechanical pathway can restore Paclitaxel sensitivity.

Area of Science:

  • Oncology
  • Biophysics
  • Cancer Biology

Background:

  • Chemotherapy resistance is a major challenge in cancer treatment, often driven by genetic mutations in a small population of resistant cells.
  • The mechanisms by which these minority-resistant cells (MRCs) drive resistance and tumor progression are not well understood.
  • Mechanical interactions between cancer cells are increasingly recognized as important factors in tumor behavior.

Purpose of the Study:

  • To investigate the mechanical pathways through which minority-resistant cancer cells (MRCs) promote drug resistance and tumor progression.
  • To explore the role of mechanical force transmission in the development and maintenance of Paclitaxel resistance.
  • To identify potential therapeutic strategies targeting mechanical interactions in cancer.

Main Methods:

  • Utilized force-induced remnant magnetization spectroscopy (FIRMS) combined with biological assays.
  • Characterized the mechanical properties of minority Paclitaxel-resistant cancer cells (MRCs) and sensitive cells (SCs).
  • Investigated the role of the force transducer Merlin in force transmission and mechano-assimilation.

Main Results:

  • Minority Paclitaxel-resistant cancer cells exhibit enhanced mechanical properties.
  • MRCs transmit high-intensity forces to surrounding SCs via Merlin, inducing 'mechano-assimilation'.
  • Mechano-assimilation accelerates drug resistance and tumor progression; its disruption restores Paclitaxel sensitivity in vitro and in vivo.

Conclusions:

  • Preliminary evidence suggests MRCs contribute to drug resistance and malignancy through mechanical interactions.
  • Mechano-assimilation is a novel mechanism driving cancer progression and resistance.
  • Targeting mechanical factors, like mechano-assimilation, offers a promising avenue for innovative cancer therapies.
Keywords:
cancer therapymechanical forcemechano‐assimilationminority Paclitaxel‐resistant cancer cellstumor microenvironment

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