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Drug Resistance in Cancers: A Free Pass for Bullying

Jing Li1, Xiao Li1, Qie Guo1

  • 1The Department of Clinical Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.

Cells
|November 11, 2022
PubMed

Insights

Cancer drug resistance stems from tumor cells adapting and becoming plastic, creating a supportive microenvironment. Understanding intratumor heterogeneity (ITH) and the tumor microenvironment (TME) offers new strategies to overcome resistance.

Area of Science:

  • Oncology
  • Cancer Biology
  • Drug Resistance Research

Background:

  • Global cancer burden is rising, with drug resistance posing a significant therapeutic challenge.
  • Tumor cells evolve resistance through genetic alterations and adaptive mechanisms, leading to intratumor heterogeneity (ITH).
  • Cellular plasticity within the tumor microenvironment (TME) enables tumor cells to adapt and resist therapies.

Purpose of the Study:

  • To re-evaluate mechanisms of drug resistance from the perspective of the TME.
  • To explore emerging themes in cancer drug resistance, including exosomes, metabolic reprogramming, protein glycosylation, and autophagy.
  • To identify novel targets and strategies for reversing drug resistance in cancers.

Main Methods:

  • Review and synthesis of recent studies on intratumor heterogeneity (ITH) and cellular plasticity.
  • Analysis of the role of the tumor microenvironment (TME) in mediating drug resistance.
  • Exploration of specific molecular mechanisms such as exosomes, metabolic reprogramming, protein glycosylation, and autophagy.

Main Results:

  • Intratumor heterogeneity (ITH) arises from genetically distinct subclones and adaptive cellular plasticity.
  • Plastic tumor cells within the TME actively modify their environment to promote proliferation and therapeutic resistance.
  • Exosomes, metabolic reprogramming, protein glycosylation, and autophagy are key adaptive mechanisms contributing to drug resistance.

Conclusions:

  • Re-evaluating drug resistance through the lens of the TME provides new insights into therapeutic challenges.
  • Targeting cellular plasticity and TME-mediated adaptations offers potential strategies to overcome cancer drug resistance.
  • Emerging themes like exosomes, metabolic reprogramming, protein glycosylation, and autophagy present novel therapeutic targets for reversing resistance.
Keywords:
autophagydrug resistanceexosomesglycosylationmetabolic reprogrammingtumor microenvironment

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