ISSN:
1573-7233
Keywords:
myelosuppression
;
therapy-related malignancy
;
chemoprotection
;
MDR-1
;
ATase
;
retrovirus
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
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 O 6-alkylguanine-DNA-alkyltransferase (ATase) gene have been used in reclinical 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00046348
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