Improvement of chemotherapy efficacy by inactivation of a DNA-repair pathway.

2.50
Hdl Handle:
http://hdl.handle.net/10541/82335
Title:
Improvement of chemotherapy efficacy by inactivation of a DNA-repair pathway.
Authors:
Middleton, Mark R; Margison, Geoffrey P
Abstract:
Tumour resistance and dose-limiting toxic effects restrict treatment with most chemotherapeutic drugs. Elucidation of the mechanisms of these effects could permit the development of ways to improve the effectiveness of currently used agents until better therapeutic agents are developed. Several types of alkylating agents are used in the treatment of cancer. The DNA repair protein, O6-alkylguanine-DNA alkyltransferase (ATase) is an important cellular resistance mechanism to one class of alkylating agents. This enzyme removes potentially lethal damage from DNA and experiments in vitro and in vivo have shown that its inactivation can reverse resistance to such agents. Clinical trials of drugs that inactivate ATase are underway and early results indicate that they are active in tumour tissues. However, the ATase present in normal tissues, particularly bone marrow, is also inactivated, necessitating a reduction in the dose of alkylating agent. An important question is whether, in the absence of any tumour-specific delivery strategy, such drugs will improve therapeutic effectiveness; initial reports are not promising.
Affiliation:
Cancer Research UK Medical Oncology Unit, Churchill Hospital, Oxford, UK.
Citation:
Improvement of chemotherapy efficacy by inactivation of a DNA-repair pathway. 2003, 4 (1):37-44 Lancet Oncol.
Journal:
The Lancet Oncology
Issue Date:
Jan-2003
URI:
http://hdl.handle.net/10541/82335
PubMed ID:
12517538
Type:
Article
Language:
en
ISSN:
1470-2045
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorMiddleton, Mark R-
dc.contributor.authorMargison, Geoffrey P-
dc.date.accessioned2009-09-23T13:16:44Z-
dc.date.available2009-09-23T13:16:44Z-
dc.date.issued2003-01-
dc.identifier.citationImprovement of chemotherapy efficacy by inactivation of a DNA-repair pathway. 2003, 4 (1):37-44 Lancet Oncol.en
dc.identifier.issn1470-2045-
dc.identifier.pmid12517538-
dc.identifier.urihttp://hdl.handle.net/10541/82335-
dc.description.abstractTumour resistance and dose-limiting toxic effects restrict treatment with most chemotherapeutic drugs. Elucidation of the mechanisms of these effects could permit the development of ways to improve the effectiveness of currently used agents until better therapeutic agents are developed. Several types of alkylating agents are used in the treatment of cancer. The DNA repair protein, O6-alkylguanine-DNA alkyltransferase (ATase) is an important cellular resistance mechanism to one class of alkylating agents. This enzyme removes potentially lethal damage from DNA and experiments in vitro and in vivo have shown that its inactivation can reverse resistance to such agents. Clinical trials of drugs that inactivate ATase are underway and early results indicate that they are active in tumour tissues. However, the ATase present in normal tissues, particularly bone marrow, is also inactivated, necessitating a reduction in the dose of alkylating agent. An important question is whether, in the absence of any tumour-specific delivery strategy, such drugs will improve therapeutic effectiveness; initial reports are not promising.en
dc.language.isoenen
dc.subjectCanceren
dc.subject.meshAnimals-
dc.subject.meshAntineoplastic Agents, Alkylating-
dc.subject.meshDNA Damage-
dc.subject.meshDNA Repair-
dc.subject.meshDrug Resistance, Neoplasm-
dc.subject.meshHumans-
dc.subject.meshNeoplasms-
dc.subject.meshNucleotidyltransferases-
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase-
dc.titleImprovement of chemotherapy efficacy by inactivation of a DNA-repair pathway.en
dc.typeArticleen
dc.contributor.departmentCancer Research UK Medical Oncology Unit, Churchill Hospital, Oxford, UK.en
dc.identifier.journalThe Lancet Oncologyen

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.