Resistance to chemotherapy in cancer: A complex and integrated cellular response

Howard R. Mellor, Richard Callaghan*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

133 Citations (Scopus)

Abstract

Inherent and acquired resistance pathways account for the high rate of failure in cancer chemotherapy. The mechanisms or pathways mediating resistance may be classified as pharmacokinetic (i.e. alter intratumour drug exposue) or pharmacodynamic (i.e. failure to elicit cytotoxicity). More often than not, the resistant phenotype is characterised by alterations in multiple pathways. Consequently, the pathways may act synergistically or generate a broad spectrum of resistance to anticancer drugs. There has been a great deal of systematic characterisation of drug resistance in vitro. However, translating this greater understanding into clinical efficacy has rarely been achieved. This review explores the phenomenon of drug resistance in cancer and highlights the gap between in vitro and in vivo observations. This gap presents a major obstacle in overcoming drug resistance and restoring sensitivity to chemotherapy.

Original languageEnglish
Pages (from-to)275-300
Number of pages26
JournalPharmacology
Volume81
Issue number4
DOIs
Publication statusPublished - May 2008
Externally publishedYes

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