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Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
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Isolation of Primary Cancer-Associated Fibroblasts from a Syngeneic Murine Model of Breast Cancer for the Study of Targeted Nanoparticles
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HIFU-Driven Targeted Pyroptosis Therapy in Basal-Like Breast Cancer.

Xiaomin Su1,2, Yang Wang1,2, Xifeng Qin3

  • 1Central Laboratory, First Affiliated Hospital, Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, 116021, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|September 14, 2025
PubMed
Summary

This study introduces a novel pyroptosis therapy for basal-like breast cancer using high-intensity focused ultrasound (HIFU) combined with mitoxantrone-loaded liposomes. This combination effectively targets tumors and triggers cell death, offering a new treatment strategy.

Keywords:
BLBCHIFUbioinformaticscathepsin Lpyroptosis

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Area of Science:

  • Biomedical Engineering
  • Oncology
  • Nanotechnology

Background:

  • Basal-like breast cancer (BLBC) presents significant treatment challenges due to its heterogeneity and lack of targeted therapies.
  • Pyroptosis, a form of programmed cell death, shows promise as a therapeutic strategy for BLBC, especially when induced by physical methods.

Purpose of the Study:

  • To develop a high-intensity focused ultrasound (HIFU)-driven targeted pyroptosis strategy for basal-like breast cancer therapy.
  • To identify synergistic pyroptosis inducers that enhance HIFU efficacy for BLBC treatment.

Main Methods:

  • Integrated HIFU-driven gene regulation analysis with TCGA bioinformatics data to identify 20 potential pyroptosis inducers.
  • Encapsulated mitoxantrone in platelet membrane-hybridized liposomes (Plp) for enhanced targeted delivery.
  • Investigated the synergistic effects of HIFU and Plp on tumor growth inhibition and pyroptosis induction in a mouse model.

Main Results:

  • The combination of HIFU and Plp significantly enhanced liposome tumor delivery (2.46-fold) and inhibited tumor growth, with 50% of mice becoming tumor-free.
  • HIFU downregulated histone deacetylases 4 and 9 while upregulating cathepsin-L (CTSL) transcription.
  • HIFU and Plp synergistically suppressed BCL-2 via CTSL, increasing ROS, activating Caspase8 and NLRP3 inflammasome, leading to pyroptosis.

Conclusions:

  • Developed an innovative pyroptosis therapy strategy by combining physical treatment (HIFU) with chemotherapy (mitoxantrone-loaded liposomes).
  • This approach offers a promising therapeutic avenue for basal-like breast cancer and potentially other refractory diseases.