Pretherapy nuclear factor-κB status, chemoradiation resistance, and metastatic progression in esophageal carcinoma

Julie G. Izzo, Arlene M. Correa, Tsung Teh Wu, Usha Malhotra, Clifford K S Chao, Rajyalakshmi Luthra, Joe Ensor, Alexander Dekovich, Zhongxing Liao, Walter N. Hittelman, Bharat B. Aggarwal, Jaffer A. Ajani

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Background: Transcriptional factor nuclear factor-κB (NF-κB) seems to be associated with aggressive clinical biology (chemoradiation resistance and metastatic progression) of esophageal cancer. We hypothesized that activated NF-κB would define clinical biology irrespective of the type of chemotherapy or sequence administered. Methods: Pretherapy and/or posttherapy cancer specimens were examined for activated NF-κB and correlated with pathologic response to chemoradiation, metastatic potential, overall survival, disease-free survival, and type of chemotherapy or sequence used. Findings: Eighty patients undergoing chemotherapy and concurrent radiation were studied. Activated NF-κB prior to any therapy was associated with the lack of complete pathologic response (pathCR, P = 0.006). Forty-five (78%) of 58 patients achieving <pathCR had activated NF-κB in pretherapy and/or posttherapy cancer specimens versus 2 (9%) of 22 patients with pathCR (P = 0.001). Twenty-four (51%) of 47 patients with activated NF-κB in cancer developed metastases versus 7 (21%) of 22 patients with negative NF-κB in cancer (P = 0.01). At a median follow-up of 32 months, 25 (53%) of 47 patients with activated NF-κB cancer had died versus 3 (9%) of 33 patients with negative NF-κB cancer. NF-κB activation was the only independent predictor of disease-free survival (P = 0.01) and overall survival (P = 0.007) in a multivariate model. The class of chemotherapy or its sequence had no effect on NF-κB expression or patient outcome. Conclusions: Our data are the first to show that pretreatment-activated NF-κB significantly correlates with clinical biology of esophageal cancer, and most importantly, with pathCR. To therapeutically exploit NF-κB-regulated genes and their pathways, further research is warranted.

Original languageEnglish (US)
Pages (from-to)2844-2850
Number of pages7
JournalMolecular Cancer Therapeutics
Volume5
Issue number11
DOIs
StatePublished - Nov 2006
Externally publishedYes

Fingerprint

Carcinoma
Drug Therapy
Neoplasms
Esophageal Neoplasms
Disease-Free Survival
Survival
Radiation
Neoplasm Metastasis
Research
Genes

ASJC Scopus subject areas

  • Oncology
  • Drug Discovery
  • Pharmacology

Cite this

Izzo, J. G., Correa, A. M., Wu, T. T., Malhotra, U., Chao, C. K. S., Luthra, R., ... Ajani, J. A. (2006). Pretherapy nuclear factor-κB status, chemoradiation resistance, and metastatic progression in esophageal carcinoma. Molecular Cancer Therapeutics, 5(11), 2844-2850. https://doi.org/10.1158/1535-7163.MCT-06-0351

Pretherapy nuclear factor-κB status, chemoradiation resistance, and metastatic progression in esophageal carcinoma. / Izzo, Julie G.; Correa, Arlene M.; Wu, Tsung Teh; Malhotra, Usha; Chao, Clifford K S; Luthra, Rajyalakshmi; Ensor, Joe; Dekovich, Alexander; Liao, Zhongxing; Hittelman, Walter N.; Aggarwal, Bharat B.; Ajani, Jaffer A.

In: Molecular Cancer Therapeutics, Vol. 5, No. 11, 11.2006, p. 2844-2850.

Research output: Contribution to journalArticle

Izzo, JG, Correa, AM, Wu, TT, Malhotra, U, Chao, CKS, Luthra, R, Ensor, J, Dekovich, A, Liao, Z, Hittelman, WN, Aggarwal, BB & Ajani, JA 2006, 'Pretherapy nuclear factor-κB status, chemoradiation resistance, and metastatic progression in esophageal carcinoma', Molecular Cancer Therapeutics, vol. 5, no. 11, pp. 2844-2850. https://doi.org/10.1158/1535-7163.MCT-06-0351
Izzo, Julie G. ; Correa, Arlene M. ; Wu, Tsung Teh ; Malhotra, Usha ; Chao, Clifford K S ; Luthra, Rajyalakshmi ; Ensor, Joe ; Dekovich, Alexander ; Liao, Zhongxing ; Hittelman, Walter N. ; Aggarwal, Bharat B. ; Ajani, Jaffer A. / Pretherapy nuclear factor-κB status, chemoradiation resistance, and metastatic progression in esophageal carcinoma. In: Molecular Cancer Therapeutics. 2006 ; Vol. 5, No. 11. pp. 2844-2850.
@article{f6f27cbc62d64047a40c16796a61f872,
title = "Pretherapy nuclear factor-κB status, chemoradiation resistance, and metastatic progression in esophageal carcinoma",
abstract = "Background: Transcriptional factor nuclear factor-κB (NF-κB) seems to be associated with aggressive clinical biology (chemoradiation resistance and metastatic progression) of esophageal cancer. We hypothesized that activated NF-κB would define clinical biology irrespective of the type of chemotherapy or sequence administered. Methods: Pretherapy and/or posttherapy cancer specimens were examined for activated NF-κB and correlated with pathologic response to chemoradiation, metastatic potential, overall survival, disease-free survival, and type of chemotherapy or sequence used. Findings: Eighty patients undergoing chemotherapy and concurrent radiation were studied. Activated NF-κB prior to any therapy was associated with the lack of complete pathologic response (pathCR, P = 0.006). Forty-five (78{\%}) of 58 patients achieving",
author = "Izzo, {Julie G.} and Correa, {Arlene M.} and Wu, {Tsung Teh} and Usha Malhotra and Chao, {Clifford K S} and Rajyalakshmi Luthra and Joe Ensor and Alexander Dekovich and Zhongxing Liao and Hittelman, {Walter N.} and Aggarwal, {Bharat B.} and Ajani, {Jaffer A.}",
year = "2006",
month = "11",
doi = "10.1158/1535-7163.MCT-06-0351",
language = "English (US)",
volume = "5",
pages = "2844--2850",
journal = "Molecular Cancer Therapeutics",
issn = "1535-7163",
publisher = "American Association for Cancer Research Inc.",
number = "11",

}

TY - JOUR

T1 - Pretherapy nuclear factor-κB status, chemoradiation resistance, and metastatic progression in esophageal carcinoma

AU - Izzo, Julie G.

AU - Correa, Arlene M.

AU - Wu, Tsung Teh

AU - Malhotra, Usha

AU - Chao, Clifford K S

AU - Luthra, Rajyalakshmi

AU - Ensor, Joe

AU - Dekovich, Alexander

AU - Liao, Zhongxing

AU - Hittelman, Walter N.

AU - Aggarwal, Bharat B.

AU - Ajani, Jaffer A.

PY - 2006/11

Y1 - 2006/11

N2 - Background: Transcriptional factor nuclear factor-κB (NF-κB) seems to be associated with aggressive clinical biology (chemoradiation resistance and metastatic progression) of esophageal cancer. We hypothesized that activated NF-κB would define clinical biology irrespective of the type of chemotherapy or sequence administered. Methods: Pretherapy and/or posttherapy cancer specimens were examined for activated NF-κB and correlated with pathologic response to chemoradiation, metastatic potential, overall survival, disease-free survival, and type of chemotherapy or sequence used. Findings: Eighty patients undergoing chemotherapy and concurrent radiation were studied. Activated NF-κB prior to any therapy was associated with the lack of complete pathologic response (pathCR, P = 0.006). Forty-five (78%) of 58 patients achieving

AB - Background: Transcriptional factor nuclear factor-κB (NF-κB) seems to be associated with aggressive clinical biology (chemoradiation resistance and metastatic progression) of esophageal cancer. We hypothesized that activated NF-κB would define clinical biology irrespective of the type of chemotherapy or sequence administered. Methods: Pretherapy and/or posttherapy cancer specimens were examined for activated NF-κB and correlated with pathologic response to chemoradiation, metastatic potential, overall survival, disease-free survival, and type of chemotherapy or sequence used. Findings: Eighty patients undergoing chemotherapy and concurrent radiation were studied. Activated NF-κB prior to any therapy was associated with the lack of complete pathologic response (pathCR, P = 0.006). Forty-five (78%) of 58 patients achieving

UR - http://www.scopus.com/inward/record.url?scp=33845217696&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845217696&partnerID=8YFLogxK

U2 - 10.1158/1535-7163.MCT-06-0351

DO - 10.1158/1535-7163.MCT-06-0351

M3 - Article

C2 - 17121931

AN - SCOPUS:33845217696

VL - 5

SP - 2844

EP - 2850

JO - Molecular Cancer Therapeutics

JF - Molecular Cancer Therapeutics

SN - 1535-7163

IS - 11

ER -