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

55 Scopus citations

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Izzo, J. G., Correa, A. M., Wu, T. T., Malhotra, U., Chao, C. K. S., Luthra, R., Ensor, J., Dekovich, A., Liao, Z., Hittelman, W. N., Aggarwal, B. B., & 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