2.50
Hdl Handle:
http://hdl.handle.net/10541/95506
Title:
Chemoprotection of normal tissues by transfer of drug resistance genes.
Authors:
Rafferty, Joseph A; Hickson, Ian; Chinnasamy, Nachimuthu; Lashford, Linda S; Margison, Geoffrey P; Dexter, T Michael; Fairbairn, Leslie J
Abstract:
The effectiveness of many types of antitumour agent is limited by (i) acute dose limiting cytotoxicity, principally myelosuppression but also lung, liver and gastrointestinal tract toxicity, (ii) the risk of therapy related secondary malignancy and (iii) the inherent or acquired drug-resistance of tumour cells. As the management of the acute toxic effects improve, the more insidious effects, and particularly haematological malignancies, are anticipated to increase. Furthermore, attempts to overcome tumour cell resistance to treatment can lead to increased collateral damage in normal tissues. One approach to circumventing both the acute toxic and chronic carcinogenic effects of chemotherapy would be to use gene therapy to achieve high levels of expression of drug resistance proteins in otherwise drug-sensitive tissues. To date the products of the multi-drug resistance (MDR-1) and the human O6-alkylguanine-DNA-alkyltransferase (ATase) gene have been used in preclinical experiments to demonstrate proof of principle, and the former of these is now being tested in a clinical situation. Here we discuss the potential of drug-resistance gene therapy to provide chemoprotection to normal tissues and examine the prospects for a dual approach which combines this with pharmacological sensitisation of tumours to chemotherapeutic agents.
Affiliation:
CRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital (NHS)-Trust, Manchester, UK.
Citation:
Chemoprotection of normal tissues by transfer of drug resistance genes. 1996, 15 (3):365-83 Cancer Metastasis Rev.
Journal:
Cancer Metastasis Reviews
Issue Date:
Sep-1996
URI:
http://hdl.handle.net/10541/95506
DOI:
10.1007/BF00046348
PubMed ID:
9034597
Type:
Article
Language:
en
ISSN:
0167-7659
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorRafferty, Joseph Aen
dc.contributor.authorHickson, Ianen
dc.contributor.authorChinnasamy, Nachimuthuen
dc.contributor.authorLashford, Linda Sen
dc.contributor.authorMargison, Geoffrey Pen
dc.contributor.authorDexter, T Michaelen
dc.contributor.authorFairbairn, Leslie Jen
dc.date.accessioned2010-04-01T15:11:04Z-
dc.date.available2010-04-01T15:11:04Z-
dc.date.issued1996-09-
dc.identifier.citationChemoprotection of normal tissues by transfer of drug resistance genes. 1996, 15 (3):365-83 Cancer Metastasis Rev.en
dc.identifier.issn0167-7659-
dc.identifier.pmid9034597-
dc.identifier.doi10.1007/BF00046348-
dc.identifier.urihttp://hdl.handle.net/10541/95506-
dc.description.abstractThe effectiveness of many types of antitumour agent is limited by (i) acute dose limiting cytotoxicity, principally myelosuppression but also lung, liver and gastrointestinal tract toxicity, (ii) the risk of therapy related secondary malignancy and (iii) the inherent or acquired drug-resistance of tumour cells. As the management of the acute toxic effects improve, the more insidious effects, and particularly haematological malignancies, are anticipated to increase. Furthermore, attempts to overcome tumour cell resistance to treatment can lead to increased collateral damage in normal tissues. One approach to circumventing both the acute toxic and chronic carcinogenic effects of chemotherapy would be to use gene therapy to achieve high levels of expression of drug resistance proteins in otherwise drug-sensitive tissues. To date the products of the multi-drug resistance (MDR-1) and the human O6-alkylguanine-DNA-alkyltransferase (ATase) gene have been used in preclinical experiments to demonstrate proof of principle, and the former of these is now being tested in a clinical situation. Here we discuss the potential of drug-resistance gene therapy to provide chemoprotection to normal tissues and examine the prospects for a dual approach which combines this with pharmacological sensitisation of tumours to chemotherapeutic agents.en
dc.language.isoenen
dc.subjectCancer Drug Resistanceen
dc.subject.meshATP-Binding Cassette Transporters-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshBone Marrow Diseases-
dc.subject.meshDrug Resistance, Multiple-
dc.subject.meshDrug Resistance, Neoplasm-
dc.subject.meshGene Transfer Techniques-
dc.subject.meshHumans-
dc.subject.meshMethyltransferases-
dc.subject.meshMultidrug Resistance-Associated Proteins-
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase-
dc.titleChemoprotection of normal tissues by transfer of drug resistance genes.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital (NHS)-Trust, Manchester, UK.en
dc.identifier.journalCancer Metastasis Reviewsen

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