Feasibility of proposed single-nucleotide polymorphisms as predictive markers for targeted regimens in metastatic colorectal cancer

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Title
Feasibility of proposed single-nucleotide polymorphisms as predictive markers for targeted regimens in metastatic colorectal cancer
Author(s)
J C Kim; Y J Ha; S A Roh; E Y Choi; Y S Yoon; K P Kim; Y S Hong; T W Kim; D H Cho; Seon-Young Kim; Yong Sung Kim
Bibliographic Citation
British Journal of Cancer, vol. 108, no. 9, pp. 1862-1869
Publication Year
2013
Abstract
Background: Surrogate biomarkers for metastatic colorectal cancer (mCRC) are urgently needed to achieve the best outcomes for targeted therapy. Methods: A clinical association analysis was performed to examine the three single-nucleotide polymorphisms (SNPs) that were previously proposed as markers of chemosensitivity to the cetuximab (124 patients) and bevacizumab regimens (100 patients) in mCRC patients. In addition, biological correlations were examined for the candidate SNPs in terms of their regulatory pathway. Results: For cetuximab regimens, patients homozygous for the wild-type alleles (GG) of LIFR rs3729740 exhibited a 1.9 times greater overall response rate (ORR) and 1.4 months longer progression-free survival (PFS) than those homozygous or heterozygous for the mutant allele (GA and AA; P=0.022 and 0.027, respectively). For bevacizumab regimens, patients homozygous for the minor alleles (TT) of ANXA11 rs1049550 exhibited an ORR twice as high as those homozygous or heterozygous for the ancestral allele (CC and CT; P=0.031). Overall response rate gain was achieved up to 10% in patients with wild-type LIFR rs3729740 patients either with wild-type KRAS or skin toxicity (P=0.001) respectively. Specifically in clones treated with cetuximab and bevacizumab regimens, active p-ERK and MMP-9 expressions were significantly reduced in clones expressing wild-type LIFR rs3729740 (P=0.044) and in those expressing minor-type ANXA11 rs1049550 (P=0.007), respectively. Conclusion: LIFR rs3729740 and possibly ANXA11 rs1049550 may be useful as biomarkers for predicting whether mCRC patients are sensitive to relevant target regimens, although further validation in large cohorts is needed.
Keyword
ANXA11 rs1049550Colorectal cancerLIFR rs3729740MarkerTargeted chemotherapy
ISSN
0007-0920
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/bjc.2013.163
Type
Article
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1. Journal Articles > Journal Articles
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