5-Fluorouracil response in a large panel of colorectal cancer cell lines is associated with mismatch repair deficiency

TY - JOUR

T1 - 5-Fluorouracil response in a large panel of colorectal cancer cell lines is associated with mismatch repair deficiency

AU - Bracht, K

AU - Nicholls, A M

AU - Liu, Ying

AU - Bodmer, W F

PY - 2010/7/27

Y1 - 2010/7/27

N2 - 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.Interpretation and conclusion: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.

AB - 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.Interpretation and conclusion: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.

KW - Antimetabolites, Antineoplastic

KW - Biocompatible Materials

KW - Cell Line, Tumor

KW - Collagen

KW - Colorectal Neoplasms

KW - DNA Mismatch Repair

KW - DNA Replication

KW - Dose-Response Relationship, Drug

KW - Drug Combinations

KW - Fluorouracil

KW - Humans

KW - Laminin

KW - Loss of Heterozygosity

KW - Mutation

KW - Proteoglycans

U2 - 10.1038/sj.bjc.6605780

DO - 10.1038/sj.bjc.6605780

M3 - Journal article

C2 - 20606684

SN - 1744-3865

VL - 103

SP - 340

EP - 346

JO - British Journal of Cancer Management

JF - British Journal of Cancer Management

IS - 3

ER -