Chemoprotection of normal tissues by transfer of drug resistance genes.
Authors
Rafferty, Joseph AHickson, Ian
Chinnasamy, Nachimuthu
Lashford, Linda S
Margison, Geoffrey P
Dexter, T Michael
Fairbairn, Leslie J
Affiliation
CRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital (NHS)-Trust, Manchester, UK.Issue Date
1996-09
Metadata
Show full item recordAbstract
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.Citation
Chemoprotection of normal tissues by transfer of drug resistance genes. 1996, 15 (3):365-83 Cancer Metastasis Rev.Journal
Cancer Metastasis ReviewsDOI
10.1007/BF00046348PubMed ID
9034597Type
ArticleLanguage
enISSN
0167-7659ae974a485f413a2113503eed53cd6c53
10.1007/BF00046348