Resistance to Chemotherapy in Cancer: A Complex and Integrated Cellular Response
- 7 February 2008
- journal article
- review article
- Published by S. Karger AG in Pharmacology
- Vol. 81 (4), 275-300
- https://doi.org/10.1159/000115967
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.Keywords
This publication has 107 references indexed in Scilit:
- Molecular basis of antifolate resistanceCancer and Metastasis Reviews, 2007
- The multifaceted mismatch-repair systemNature Reviews Molecular Cell Biology, 2006
- Apoptosis effector mechanisms: A requiem performed in different keysApoptosis, 2006
- The response to cyclophosphamide in steroid-sensitive nephrotic syndrome is influenced by polymorphic expression of glutathion-S-transferases-M1 and -P1Pediatric Nephrology, 2005
- Improved penetration of docetaxel into the brain by co-administration of inhibitors of P-glycoproteinEuropean Journal of Cancer, 2004
- Molecular prognostic markers in pancreatic cancerJournal of Hepato-Biliary-Pancreatic Surgery, 2002
- Multidrug resistance in cancer: role of ATP–dependent transportersNature Reviews Cancer, 2002
- Hypoxia — a key regulatory factor in tumour growthNature Reviews Cancer, 2002
- MDR1/P-glycoprotein in haematological neoplasmsEuropean Journal of Cancer, 1996
- Antiproliferative activity of vinorelbine (Navelbine) against six human melanoma cell linesZeitschrift für Krebsforschung und Klinische Onkologie, 1992