PMID- 20443891
OWN - NLM
STAT- MEDLINE
DCOM- 20100730
LR  - 20211020
IS  - 1752-8062 (Electronic)
IS  - 1752-8054 (Print)
IS  - 1752-8054 (Linking)
VI  - 2
IP  - 3
DP  - 2009 Jun
TI  - Identification of biomarkers in human head and neck tumor cell lines that predict 
      for in vitro sensitivity to gefitinib.
PG  - 183-92
LID - 10.1111/j.1752-8062.2009.00099.x [doi]
AB  - Potential biomarkers were identified for in vitro sensitivity to the epidermal 
      growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib in head and 
      neck cancer. Gefitinib sensitivity was determined in cell lines, followed by 
      transcript profiling coupled with a novel pathway analysis approach. Eleven cell 
      lines were highly sensitive to gefitinib (inhibitor concentration required to 
      give 50% growth inhibition [GI(50)] < 1 microM), three had intermediate 
      sensitivity (GI(50) 1-7 microM), and six were resistant (GI(50) > 7 microM); an 
      exploratory principal component analysis revealed a separation between the 
      genomic profiles of sensitive and resistant cell lines. Subsequently, a 
      hypothesis-driven analysis of Affymetrix data (Affymetrix, Inc., Santa Clara, CA, 
      USA) revealed higher mRNA levels for E-cadherin (CDH1); transforming growth 
      factor, alpha (TGF-alpha); amphiregulin (AREG); FLJ22662; EGFR; p21-activated 
      kinase 6 (PAK6); glutathione S-transferase Pi (GSTP1); and ATP-binding cassette, 
      subfamily C, member 5 (ABCC5) in sensitive versus resistant cell lines. A 
      hypothesis-free analysis identified 46 gene transcripts that were strongly 
      differentiated, seven of which had a known association with EGFR and head and 
      neck cancer (human EGF receptor 3 [HER3], TGF-alpha, CDH1, EGFR, keratin 16 
      [KRT16], fibroblast growth factor 2 [FGF2], and cortactin [CTTN]). Polymerase 
      chain reaction (PCR) and enzyme-linked immunoabsorbant assay analysis confirmed 
      Affymetrix data, and EGFR gene mutation, amplification, and genomic gain 
      correlated strongly with gefitinib sensitivity. We identified biomarkers that 
      predict for in vitro responsiveness to gefitinib, seven of which have known 
      association with EGFR and head and neck cancer. These in vitro predictive 
      biomarkers may have potential utility in the clinic and warrant further 
      investigation.
FAU - Hickinson, D Mark
AU  - Hickinson DM
AD  - Fomerly of AstraZeneca, Alderly Park, Macclesfield, UK.
FAU - Marshall, Gayle B
AU  - Marshall GB
FAU - Beran, Garry J
AU  - Beran GJ
FAU - Varella-Garcia, Marileila
AU  - Varella-Garcia M
FAU - Mills, Elizabeth A
AU  - Mills EA
FAU - South, Marie C
AU  - South MC
FAU - Cassidy, Andrew M
AU  - Cassidy AM
FAU - Acheson, Kerry L
AU  - Acheson KL
FAU - McWalter, Gael
AU  - McWalter G
FAU - McCormack, Rose M
AU  - McCormack RM
FAU - Bunn, Paul A
AU  - Bunn PA
FAU - French, Tim
AU  - French T
FAU - Graham, Alex
AU  - Graham A
FAU - Holloway, Brian R
AU  - Holloway BR
FAU - Hirsch, Fred R
AU  - Hirsch FR
FAU - Speake, Georgina
AU  - Speake G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Transl Sci
JT  - Clinical and translational science
JID - 101474067
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Quinazolines)
RN  - 0 (RNA, Messenger)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology/therapeutic use
MH  - Biomarkers, Tumor/*analysis/genetics
MH  - Cell Line, Tumor
MH  - DNA Mutational Analysis
MH  - Drug Resistance, Neoplasm/*drug effects/genetics
MH  - Drug Screening Assays, Antitumor
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Gefitinib
MH  - Gene Dosage/genetics
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Genome, Human/genetics
MH  - Head and Neck Neoplasms/*genetics
MH  - Humans
MH  - Neoplasm Proteins/genetics/metabolism
MH  - Quinazolines/*pharmacology/therapeutic use
MH  - RNA, Messenger/genetics/metabolism
PMC - PMC5350732
EDAT- 2010/05/07 06:00
MHDA- 2010/07/31 06:00
PMCR- 2009/06/01
CRDT- 2010/05/07 06:00
PHST- 2010/05/07 06:00 [entrez]
PHST- 2010/05/07 06:00 [pubmed]
PHST- 2010/07/31 06:00 [medline]
PHST- 2009/06/01 00:00 [pmc-release]
AID - CTS099 [pii]
AID - 10.1111/j.1752-8062.2009.00099.x [doi]
PST - ppublish
SO  - Clin Transl Sci. 2009 Jun;2(3):183-92. doi: 10.1111/j.1752-8062.2009.00099.x.