Pretherapy nuclear factor-kappaB status, chemoradiation resistance, and metastatic progression in esophageal carcinoma.
BACKGROUND: Transcriptional factor nuclear factor-kappaB (NF-kappaB) seems to be associated with aggressive clinical biology (chemoradiation resistance and metastatic progression) of esophageal cancer. We hypothesized that activated NF-kappaB 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-kappaB 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-kappaB 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-kappaB 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-kappaB in cancer developed metastases versus 7 (21%) of 22 patients with negative NF-kappaB in cancer (P = 0.01). At a median follow-up of 32 months, 25 (53%) of 47 patients with activated NF-kappaB cancer had died versus 3 (9%) of 33 patients with negative NF-kappaB cancer. NF-kappaB 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-kappaB expression or patient outcome. CONCLUSIONS: Our data are the first to show that pretreatment-activated NF-kappaB significantly correlates with clinical biology of esophageal cancer, and most importantly, with pathCR. To therapeutically exploit NF-kappaB-regulated genes and their pathways, further research is warranted.[1]References
- Pretherapy nuclear factor-kappaB status, chemoradiation resistance, and metastatic progression in esophageal carcinoma. Izzo, J.G., Correa, A.M., Wu, T.T., Malhotra, U., Chao, C.K., Luthra, R., Ensor, J., Dekovich, A., Liao, Z., Hittelman, W.N., Aggarwal, B.B., Ajani, J.A. Mol. Cancer Ther. (2006) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
