PMID- 21206494
OWN - NLM
STAT- MEDLINE
DCOM- 20110321
LR  - 20211020
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 104
IP  - 3
DP  - 2011 Feb 1
TI  - Tumour gene expression predicts response to cetuximab in patients with KRAS 
      wild-type metastatic colorectal cancer.
PG  - 488-95
LID - 10.1038/sj.bjc.6606054 [doi]
AB  - BACKGROUND: Although it is accepted that metastatic colorectal cancers (mCRCs) 
      that carry activating mutations in KRAS are unresponsive to anti-epidermal growth 
      factor receptor (EGFR) monoclonal antibodies, a significant fraction of KRAS 
      wild-type (wt) mCRCs are also unresponsive to anti-EGFR therapy. Genes encoding 
      EGFR ligands amphiregulin (AREG) and epiregulin (EREG) are promising gene 
      expression-based markers but have not been incorporated into a test to 
      dichotomise KRAS wt mCRC patients with respect to sensitivity to anti-EGFR 
      treatment. METHODS: We used RT-PCR to test 110 candidate gene expression markers 
      in primary tumours from 144 KRAS wt mCRC patients who received monotherapy with 
      the anti-EGFR antibody cetuximab. Results were correlated with multiple clinical 
      endpoints: disease control, objective response, and progression-free survival 
      (PFS). RESULTS: Expression of many of the tested candidate genes, including EREG 
      and AREG, strongly associate with all clinical endpoints. Using multivariate 
      analysis with two-layer five-fold cross-validation, we constructed a four-gene 
      predictive classifier. Strikingly, patients below the classifier cutpoint had PFS 
      and disease control rates similar to those of patients with KRAS mutant mCRC. 
      CONCLUSION: Gene expression appears to identify KRAS wt mCRC patients who receive 
      little benefit from cetuximab. It will be important to test this model in an 
      independent validation study.
FAU - Baker, J B
AU  - Baker JB
AD  - Genomic Health, Inc., 301 Penobscot Drive, Redwood City, CA, USA.
FAU - Dutta, D
AU  - Dutta D
FAU - Watson, D
AU  - Watson D
FAU - Maddala, T
AU  - Maddala T
FAU - Munneke, B M
AU  - Munneke BM
FAU - Shak, S
AU  - Shak S
FAU - Rowinsky, E K
AU  - Rowinsky EK
FAU - Xu, L-A
AU  - Xu LA
FAU - Harbison, C T
AU  - Harbison CT
FAU - Clark, E A
AU  - Clark EA
FAU - Mauro, D J
AU  - Mauro DJ
FAU - Khambata-Ford, S
AU  - Khambata-Ford S
LA  - eng
PT  - Journal Article
DEP - 20110104
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (KRAS protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - EC 3.6.5.2 (ras Proteins)
RN  - PQX0D8J21J (Cetuximab)
SB  - IM
MH  - Antibodies, Monoclonal/therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Agents/therapeutic use
MH  - Cetuximab
MH  - Colorectal Neoplasms/*drug therapy/*genetics/secondary
MH  - Drug Resistance, Neoplasm/genetics
MH  - Gene Expression
MH  - Humans
MH  - Proto-Oncogene Proteins/*genetics
MH  - Proto-Oncogene Proteins p21(ras)
MH  - ras Proteins/*genetics
PMC - PMC3049558
COIS- The authors are employees of the respective companies listed.
EDAT- 2011/01/06 06:00
MHDA- 2011/03/22 06:00
PMCR- 2011/02/01
CRDT- 2011/01/06 06:00
PHST- 2011/01/06 06:00 [entrez]
PHST- 2011/01/06 06:00 [pubmed]
PHST- 2011/03/22 06:00 [medline]
PHST- 2011/02/01 00:00 [pmc-release]
AID - 6606054 [pii]
AID - 10.1038/sj.bjc.6606054 [doi]
PST - ppublish
SO  - Br J Cancer. 2011 Feb 1;104(3):488-95. doi: 10.1038/sj.bjc.6606054. Epub 2011 Jan 
      4.