Reduction of cellular cisplatin resistance by hyperthermia - a review

JVE Hettinga, AWT Konings, HH Kampinga

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    84 Citations (Scopus)

    Abstract

    Resistance to cisplatin (cDDP) is a major limitation to its clinical effectiveness. Review of literature data indicates that cDDP resistance is a multifactorial phenomenon. This provides an explanation why attempts to reverse or circumvent resistance using cDDP-analogues or combination therapy with modulators of specific resistance mechanisms have had limited success so far. It therefore provides a rationale to use hyperthermia, an agent with pleiotropic effects on cells, in trying to modulate cDDP resistance. In this review the effects of hyperthermia on cDDP cytotoxicity and resistance as well as underlying mechanisms are discussed. Hyperthermia is found to be a powerful modulator of cDDP cytotoxicity, both in sensitive and resistant cells. Relatively high heat doses (60 min 43 degrees C) seem to specifically interfere with cDDP resistance. The mechanism of interaction has not been fully elucidated so far, but seems to consist of multiple (simultaneous) effects on drug accumulation, adduct-formation and -repair. This may explain why hyperthermia seems to be so effective in increasing cDDP cytotoxicity, irrespective of the presence of resistance mechanisms. Therefore, the combination of hyperthermia and cDDP deserves further attention.

    Original languageEnglish
    Pages (from-to)439-457
    Number of pages19
    JournalInternational journal of hyperthermia
    Volume13
    Issue number5
    Publication statusPublished - 1997

    Keywords

    • thermochemosensitization
    • cDDP resistance
    • reversal of resistance
    • mechanism of sensitization
    • review
    • HUMAN OVARIAN-CANCER
    • TRANSCRIPTIONALLY ACTIVE GENES
    • CROSS-LINKING AGENTS
    • ENHANCED DNA-REPAIR
    • EXCISION REPAIR
    • DRUG-RESISTANCE
    • CYTO-TOXICITY
    • REGIONAL HYPERTHERMIA
    • ACQUIRED-RESISTANCE
    • THERMAL ENHANCEMENT

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