Linked Life Data

7642470

Source:http://linkedlifedata.com/resource/pubmed/id/7642470

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1995-9-15
pubmed:abstractText
Antimetabolites are rational agents with specific S-phase and enzyme targets. Low levels of target enzymes in tumors are associated with innate drug sensitivity, and the general requirement for transport and metabolic activation of antimetabolites creates several loci of acquired drug resistance. Pharmacodynamic studies of TS inhibition after fluoropyrimidines clearly can predict for tumor sensitivity and response to fluoropyrimidine-based therapy or identify factors related to resistance, and ara-dCTP levels in leukemic cells can be useful for refined dosing of araC. Powerful new DHFR and TS directed agents are in advanced levels of clinical evaluation, and purine analogues directed against adenosine deaminase are newly available for treatment of indolent lymphomas. Progress in analysis of tumors, such as PCR techniques to study gene expression or immunostaining of target enzymes, offer increasing promise for individualization of patient selection. Increased experience with biochemical modulators, including biologic response modifiers, has opened the possibility for selective attack on specific mechanisms of drug resistance. Sophisticated pharmacokinetic modeling and pharmacogenetic testing of metabolic phenotypes can now be done to achieve optimal dosing with less risk of toxicity. Considerations of ultimate genetic mechanisms of antimetabolite effects, especially by programmed cell death, and relationships to mechanisms of cell cycle regulation offer exciting rationales for future drug development.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0889-8588
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
397-413
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Clinical resistance to antimetabolites.
pubmed:affiliation
Department of Medicine, University of Southern California School of Medicine, Los Angeles, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review