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Targeted Cancer Therapies02:57

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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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Related Experiment Video

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Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NF&#954;B Activity and Breast Cancer Stem Cells
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PLGA-Nano-Encapsulated Disulfiram Inhibits Cancer Stem Cells and Targets Non-Small Cell Lung Cancer In Vitro and In

Kate Butcher1,2, Zhipeng Wang1, Sathishkumar Kurusamy1,3

  • 1Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK.

Biomolecules
|January 8, 2025
PubMed
Summary

Hypoxia promotes cancer stem cell traits and drug resistance in non-small cell lung cancer (NSCLC). The drug disulfiram, delivered via nanoparticles, effectively combats these resistant NSCLC cells, offering a promising new therapeutic strategy.

Keywords:
PLGA nano-deliverycancer stem cellschemoresistancecopper gluconatedisulfiramnon-small cell lung cancer

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Area of Science:

  • Oncology
  • Cancer Biology
  • Pharmacology

Background:

  • Cancer stem cells (CSCs) are crucial drivers of non-small cell lung cancer (NSCLC) chemoresistance and metastasis.
  • Hypoxia is implicated in maintaining CSC traits and drug resistance.

Purpose of the Study:

  • To investigate the role of hypoxia in inducing and maintaining CSC traits in NSCLC.
  • To evaluate the anti-CSC effects of disulfiram (DS) and its nanoparticle formulation (DS-PLGA).

Main Methods:

  • Utilized two NSCLC cell lines to study hypoxia-induced stemness and chemoresistance.
  • Investigated the role of the NF-κB pathway.
  • Assessed the in vitro and in vivo efficacy of disulfiram and DS-PLGA, including combination therapy with copper gluconate.

Main Results:

  • Hypoxia significantly induced stemness and chemoresistance in NSCLC cells.
  • Disulfiram demonstrated potent in vitro anti-CSC activity, blocking sphere formation and enhancing chemotherapy drug efficacy.
  • DS-PLGA combined with copper gluconate showed significant anticancer efficacy in a metastatic NSCLC mouse model.

Conclusions:

  • Hypoxia-induced stemness and chemoresistance in NSCLC are mediated by pathways including NF-κB.
  • Disulfiram, particularly in a nanoparticle formulation (DS-PLGA) with copper, presents a promising therapeutic strategy against NSCLC CSCs and metastasis.