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Understanding Cancer's Defense against Topoisomerase-Active Drugs: A Comprehensive Review

Nilesh Kumar Sharma1, Anjali Bahot1, Gopinath Sekar1

  • 1Cancer and Translational Research Centre Dr. D.Y. Patil Biotechnology & Bioinformatics Institute, Dr. D.Y. Patil Vidyapeeth, Pune 411033, Maharashtra, India.

Cancers
|February 24, 2024
PubMed

Insights

Cancer drug resistance, driven by tumor complexity, hinders treatments like topoisomerase-active drugs. Understanding resistance mechanisms and exploring drug combinations can improve cancer therapy outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Cancer drug resistance is a major challenge, characterized by genetic heterogeneity and cellular complexities.
  • Mechanisms include oxidative stress, immune evasion, metabolic reprogramming, ABC transporter overexpression, and cancer stem cell properties.
  • Topoisomerase-active drugs (e.g., doxorubicin, topotecan) are vital but often face resistance, leading to therapeutic failure.

Purpose of the Study:

  • To comprehensively review the intricate molecular and cellular mechanisms of resistance to topoisomerase-active drugs.
  • To explore potential combinatorial strategies involving topoisomerase-active drugs and resistance pathway inhibitors.

Main Methods:

  • Literature review and synthesis of current research on cancer drug resistance mechanisms.
  • Analysis of intracellular and extracellular resistance pathways.
  • Evaluation of combinatorial therapeutic approaches.

Main Results:

  • Detailed elucidation of diverse resistance mechanisms to topoisomerase-active agents.
  • Identification of key pathways contributing to drug resistance.
  • Discussion of synergistic potential of combination therapies.

Conclusions:

  • A deeper understanding of resistance mechanisms is crucial for overcoming therapeutic limitations.
  • Combinatorial strategies hold promise for enhancing the efficacy of topoisomerase-active drugs.
  • Interdisciplinary approaches are essential for developing effective, resistance-transcending cancer treatments.
Keywords:
combinatorial approachesdrug resistancemolecular heterogeneityneoplasmstopoisomerases

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