caa a22 4500 47703778X CHVBK 20180405111309.0 cr unu---uuuuu 170330e19960901xx s 000 0 eng 10.1007/BF00046348 doi (NATIONALLICENCE)springer-10.1007/BF00046348 Chemoprotection of normal tissues by transfer of drug resistance genes [Elektronische Daten] [J. Rafferty, I. Hickson, N. Chinnasamy, L. Lashford, G. Margison, T. Dexter, L. Fairbairn] 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. Kluwer Academic Publishers, 1996 myelosuppression nationallicence therapy-related malignancy nationallicence chemoprotection nationallicence MDR-1 nationallicence ATase nationallicence retrovirus nationallicence Rafferty J. CRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital (NHS)-Trust, M20 9BX, Manchester, UK aut Hickson I. CRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital (NHS)-Trust, M20 9BX, Manchester, UK aut Chinnasamy N. CRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital (NHS)-Trust, M20 9BX, Manchester, UK aut Lashford L. CRC Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital (NHS)-Trust, M20 9BX, Manchester, UK aut Margison G. CRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital (NHS)-Trust, M20 9BX, Manchester, UK aut Dexter T. CRC Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital (NHS)-Trust, M20 9BX, Manchester, UK aut Fairbairn L. CRC Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital (NHS)-Trust, M20 9BX, Manchester, UK aut Cancer and Metastasis Reviews Kluwer Academic Publishers 15/3(1996-09-01), 365-383 0167-7659 15:3<365 1996 15 10555 https://doi.org/10.1007/BF00046348 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00046348 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Rafferty J. CRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital (NHS)-Trust, M20 9BX, Manchester, UK aut NATIONALLICENCE 700 1- Hickson I. CRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital (NHS)-Trust, M20 9BX, Manchester, UK aut NATIONALLICENCE 700 1- Chinnasamy N. CRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital (NHS)-Trust, M20 9BX, Manchester, UK aut NATIONALLICENCE 700 1- Lashford L. CRC Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital (NHS)-Trust, M20 9BX, Manchester, UK aut NATIONALLICENCE 700 1- Margison G. CRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital (NHS)-Trust, M20 9BX, Manchester, UK aut NATIONALLICENCE 700 1- Dexter T. CRC Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital (NHS)-Trust, M20 9BX, Manchester, UK aut NATIONALLICENCE 700 1- Fairbairn L. CRC Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital (NHS)-Trust, M20 9BX, Manchester, UK aut NATIONALLICENCE 773 0- Cancer and Metastasis Reviews Kluwer Academic Publishers 15/3(1996-09-01), 365-383 0167-7659 15:3<365 1996 15 10555 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer