Abstract
Strategies that are selective for eradicating methotrexate resistant cells are described. These strategies have been developed based on knowledge of the mechanism of drug resistance encountered in experimental systems and in the clinic. Drug resistance to methotrexate in experimental tumors is commonly due to either gene amplification (dihydrofolate reductase) or to impaired transport of methotrexate. While no effective drugs or methods to prevent gene amplification have been described, the concept of developing "pro drugs", i.e. a drug that is selectively reduced by dihydrofolate reductase to an inhibitor of another critical folate enzyme (thymidylate synthase, methionine synthetase, folylpolyglutamte synthetase) remains worthwhile. Second generation antifolates such as trimetrexate which are effective vs methotrexate transport resistant cells have already been developed and are in clinical trial.
| Original language | English |
|---|---|
| Pages (from-to) | 3-11 |
| Number of pages | 9 |
| Journal | Advances in Enzyme Regulation |
| Volume | 24 |
| Issue number | C |
| DOIs | |
| Publication status | Published - 1985 |
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ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
Cite this
Methotrexate resistant cells at targets for selective chemotherapy. / Bertino, J. R.; Mini, E.; Sobrero, A.; Moroson, B. A.; Love, T.; Jastreboff, M.; Carmen, M.; Srimatkandada, S.; Dube, S.
In: Advances in Enzyme Regulation, Vol. 24, No. C, 1985, p. 3-11.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Methotrexate resistant cells at targets for selective chemotherapy
AU - Bertino, J. R.
AU - Mini, E.
AU - Sobrero, A.
AU - Moroson, B. A.
AU - Love, T.
AU - Jastreboff, M.
AU - Carmen, M.
AU - Srimatkandada, S.
AU - Dube, S.
PY - 1985
Y1 - 1985
N2 - Strategies that are selective for eradicating methotrexate resistant cells are described. These strategies have been developed based on knowledge of the mechanism of drug resistance encountered in experimental systems and in the clinic. Drug resistance to methotrexate in experimental tumors is commonly due to either gene amplification (dihydrofolate reductase) or to impaired transport of methotrexate. While no effective drugs or methods to prevent gene amplification have been described, the concept of developing "pro drugs", i.e. a drug that is selectively reduced by dihydrofolate reductase to an inhibitor of another critical folate enzyme (thymidylate synthase, methionine synthetase, folylpolyglutamte synthetase) remains worthwhile. Second generation antifolates such as trimetrexate which are effective vs methotrexate transport resistant cells have already been developed and are in clinical trial.
AB - Strategies that are selective for eradicating methotrexate resistant cells are described. These strategies have been developed based on knowledge of the mechanism of drug resistance encountered in experimental systems and in the clinic. Drug resistance to methotrexate in experimental tumors is commonly due to either gene amplification (dihydrofolate reductase) or to impaired transport of methotrexate. While no effective drugs or methods to prevent gene amplification have been described, the concept of developing "pro drugs", i.e. a drug that is selectively reduced by dihydrofolate reductase to an inhibitor of another critical folate enzyme (thymidylate synthase, methionine synthetase, folylpolyglutamte synthetase) remains worthwhile. Second generation antifolates such as trimetrexate which are effective vs methotrexate transport resistant cells have already been developed and are in clinical trial.
UR - http://www.scopus.com/inward/record.url?scp=0022238898&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0022238898&partnerID=8YFLogxK
U2 - 10.1016/0065-2571(85)90066-4
DO - 10.1016/0065-2571(85)90066-4
M3 - Article
C2 - 3915186
AN - SCOPUS:0022238898
VL - 24
SP - 3
EP - 11
JO - Advances in Enzyme Regulation
JF - Advances in Enzyme Regulation
SN - 0065-2571
IS - C
ER -