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Resistance to Chemotherapy in Cancer: A Complex and Integrated Cellular Response

Date

2008

Authors

Mellor, Howard R.
Callaghan, Richard

Journal Title

Journal ISSN

Volume Title

Publisher

S. Karger AG

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.

Description

Keywords

Keywords: anthracycline; bleomycin; carboplatin; carmustine; cisplatin; cyclophosphamide; daunorubicin; dj 927; docetaxel; doxorubicin; elacridar; epirubicin; fluorouracil; gemcitabine; hycamptin; idarubicin; ifosfamide; irinotecan; lomeguatrib; methotrexate; mitom Anticancer drugs; Cancer chemotherapy; Drug resistance; Multidrug resistance; Pharmacodynamic resistance; Pharmacokinetic resistance

Citation

Source

Pharmacology

Type

Journal article

Book Title

Entity type

Access Statement

License Rights

DOI

10.1159/000115967

Restricted until

2037-12-31