PMID- 18303430
OWN - NLM
STAT- MEDLINE
DCOM- 20080416
LR  - 20220224
IS  - 1556-1380 (Electronic)
IS  - 1556-0864 (Linking)
VI  - 3
IP  - 2
DP  - 2008 Feb
TI  - Tumor response to combination celecoxib and erlotinib therapy in non-small cell 
      lung cancer is associated with a low baseline matrix metalloproteinase-9 and a 
      decline in serum-soluble E-cadherin.
PG  - 117-24
LID - 10.1097/JTO.0b013e3181622bef [doi]
AB  - INTRODUCTION: Cyclooxygenase-2 overexpression may mediate resistance to epidermal 
      growth factor receptor tyrosine kinase inhibition through prostaglandin 
      E2-dependent promotion of epithelial to mesenchymal transition (EMT). Suppression 
      of epithelial markers, such as E-cadherin, can lead to resistance to erlotinib. 
      Prostaglandin E2 down-regulates E-cadherin expression by up-regulating 
      transcriptional repressors, including ZEB1 and Snail. Furthermore, E-cadherin can 
      be modulated by matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs 
      (TIMPs), promoting tumor invasion and metastasis. Markers of EMT and tumor 
      invasion were evaluated in patient serum from a phase I clinical trial 
      investigating the combination of celecoxib and erlotinib in non-small cell lung 
      cancer (NSCLC) patients. METHODS: Samples from 22 subjects were evaluated. 
      Soluble E-cadherin (sEC) was evaluated by enzyme linked immunosorbent assay in 
      patient serum at baseline, week 4, and week 8 of treatment. Other markers of EMT 
      and angiogenesis were evaluated by enzyme linked immunosorbent assay, including 
      MMP-9, TIMP-1, and CCL15. RESULTS: Serum sEC, MMP-9, TIMP-1, and CCL15 levels 
      were determined at baseline and week 8. Patients with a partial response to 
      therapy had a significant decrease in sEC, TIMP-1, and CCL15 at week 8. In 
      patients who responded to the combination therapy, baseline MMP-9 was 
      significantly lower compared with nonresponders (p = 0.006). CONCLUSIONS: sEC, 
      MMP-9, TIMP-1, and CCL15 levels correlate with response to combination therapy 
      with erlotinib and celecoxib in patients with NSCLC. A randomized phase II trial 
      is planned comparing erlotinib and celecoxib with erlotinib plus placebo in 
      advanced NSCLC. This study will prospectively assess these and other biomarkers 
      in serum and tumor tissue.
FAU - Reckamp, Karen L
AU  - Reckamp KL
AD  - Department of Medical Oncology and Therapeutics Research, City of Hope and 
      Beckman Research Institute, Duarte, California, USA. kreckamp@coh.org
FAU - Gardner, Brian K
AU  - Gardner BK
FAU - Figlin, Robert A
AU  - Figlin RA
FAU - Elashoff, David
AU  - Elashoff D
FAU - Krysan, Kostyantyn
AU  - Krysan K
FAU - Dohadwala, Mariam
AU  - Dohadwala M
FAU - Mao, Jenny
AU  - Mao J
FAU - Sharma, Sherven
AU  - Sharma S
FAU - Inge, Landon
AU  - Inge L
FAU - Rajasekaran, Ayyappan
AU  - Rajasekaran A
FAU - Dubinett, Steven M
AU  - Dubinett SM
LA  - eng
GR  - P50CA90388/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Thorac Oncol
JT  - Journal of thoracic oncology : official publication of the International 
      Association for the Study of Lung Cancer
JID - 101274235
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CCL15 protein, human)
RN  - 0 (Cadherins)
RN  - 0 (Chemokines, CC)
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Macrophage Inflammatory Proteins)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrazoles)
RN  - 0 (Quinazolines)
RN  - 0 (Sulfonamides)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - DA87705X9K (Erlotinib Hydrochloride)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - JCX84Q7J1L (Celecoxib)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/*pharmacology/therapeutic use
MH  - Biomarkers, Tumor/*blood
MH  - Cadherins/*blood
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy
MH  - Celecoxib
MH  - Chemokines, CC/blood
MH  - Cyclooxygenase Inhibitors/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - *Drug Resistance, Neoplasm
MH  - ErbB Receptors/antagonists & inhibitors
MH  - Erlotinib Hydrochloride
MH  - Humans
MH  - Lung Neoplasms/*drug therapy
MH  - Macrophage Inflammatory Proteins/blood
MH  - Matrix Metalloproteinase 9/*blood
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Pyrazoles/administration & dosage/pharmacology
MH  - Quinazolines/administration & dosage/pharmacology
MH  - Sulfonamides/administration & dosage/pharmacology
MH  - Tissue Inhibitor of Metalloproteinase-1/blood
EDAT- 2008/02/28 09:00
MHDA- 2008/04/17 09:00
CRDT- 2008/02/28 09:00
PHST- 2008/02/28 09:00 [pubmed]
PHST- 2008/04/17 09:00 [medline]
PHST- 2008/02/28 09:00 [entrez]
AID - S1556-0864(15)31407-6 [pii]
AID - 10.1097/JTO.0b013e3181622bef [doi]
PST - ppublish
SO  - J Thorac Oncol. 2008 Feb;3(2):117-24. doi: 10.1097/JTO.0b013e3181622bef.