Molecular pharmacology of cancer therapy in human colorectal cancer by gene expression profiling.
Global gene expression profiling has potential for elucidating the complex cellular effects and mechanisms of action of novel targeted anticancer agents or existing chemotherapeutics for which the precise molecular mechanism of action may be unclear. In this study, decreased expression of genes required for RNA and protein synthesis, and for metabolism were detected in rectal cancer biopsies taken from patients during a 5-fluorouracil infusion. Our observations demonstrate that this approach is feasible and can detect responses that may have otherwise been missed by conventional methods. The results suggested new mechanism-based combination treatments for colorectal cancer and demonstrated that expression profiling could provide valuable information on the molecular pharmacology of established and novel drugs.
Clarke
Paul A
PA
Cancer Research UK Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey SM2 5NG. Paul.Clarke@icr.ac.uk
George
Mark L
ML
Easdale
Sandra
S
Cunningham
David
D
Swift
R Ian
RI
Hill
Mark E
ME
Tait
Diana M
DM
Workman
Paul
P
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors
D012333:RNA, Messenger; D016685:Mitomycin; D013940:Thymidylate Synthase; D005472:Fluorouracil