5-Fluorouracil response in a large panel of colorectal cancer cell lines is associated with mismatch repair deficiency.
BACKGROUND
Colorectal cancer is (CRC) one of the commonest cancers and its therapy is still based on few drugs. Currently, no biological criteria are used to choose the most effective of the established drugs for treatment.


METHODS
A panel of 77 CRC cell lines was tested for sensitivity to 5-fluorouracil (5FU) using the SRB assay. The responses were grouped into three categories and correlated with genetic changes in the cell lines.


RESULTS
The strongest and most clearcut correlation was between 5-fluorouracil response and replication error status (mismatch repair deficiency). All the other significant correlations (loss of heterozygosity for DCC and mutations in TGFbIIR) are secondary to the association with replication error status.


CONCLUSIONS
Our findings validate previous analyses based mainly on clinical data, and indicate that replication error status could be a useful guide to 5-fluorouracil-based CRC therapy. Essentially, all previously described correlations with 5FU response are secondary to the association with replication error status.
Bracht
K
K
Cancer Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK.
Nicholls
A M
AM
Liu
Y
Y
Bodmer
W F
WF
D000964:Antimetabolites, Antineoplastic / Q000633:toxicity; D001672:Biocompatible Materials; D045744:Cell Line, Tumor / Q000187:drug effects*; D003094:Collagen; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D053843:DNA Mismatch Repair / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005472:Fluorouracil / Q000633:toxicity*; D006801:Humans; D007797:Laminin; D019656:Loss of Heterozygosity / Q000187:drug effects; D009154:Mutation; D011509:Proteoglycans
D000964:Antimetabolites, Antineoplastic; D001672:Biocompatible Materials; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D005472:Fluorouracil