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The extended-MDR phenotype

R Davey1, M Davey

  • 1Clinical Oncology Department, Royal North Shore Hospital, Bill Walsh Cancer Research Laboratories, St. Leonards, 2065, Australia., rdavey@med.usyd.edu.au.

Cytotechnology
|November 13, 2008
PubMed

Insights

Cellular models reveal extended multidrug resistance (MDR) mechanisms. Low-dose, intermittent chemotherapy can generate broad drug cross resistance, mimicking clinical cancer treatment failure.

Area of Science:

  • Molecular biology
  • Cancer research
  • Pharmacology

Background:

  • Cellular models are crucial for understanding chemotherapy drug resistance mechanisms.
  • Existing models often use high drug doses, generating multidrug resistance (MDR) but not broad cross-resistance seen in refractory cancers.
  • A subset of models exhibits resistance to diverse drug classes, including natural products, alkylating agents, and antimetabolites.

Purpose of the Study:

  • To review factors promoting extended multidrug resistance (MDR).
  • To characterize cell sublines exhibiting extended MDR.
  • To explore potential resistance mechanisms involved in extended MDR.

Main Methods:

  • Review of existing literature on cellular models of drug resistance.
  • Analysis of studies reporting cell sublines with broad drug cross-resistance.
  • Identification of common features in the generation and characteristics of extended-MDR sublines.

Main Results:

  • Extended multidrug resistance (MDR) can be generated by intermittent exposure to low, clinically relevant drug doses.
  • These models display resistance beyond typical MDR, including to alkylating agents and antimetabolites.
  • The development of extended MDR is influenced by specific treatment protocols and cellular responses.

Conclusions:

  • Cellular models generated with low-dose, intermittent chemotherapy better recapitulate clinical multidrug resistance (MDR) phenotypes.
  • Understanding extended MDR is vital for developing strategies to overcome treatment failure in cancer.
  • Further research into the molecular mechanisms underlying extended MDR is warranted.

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