NF- κ B is activated by radiotherapy and is prognostic for overall survival in patients with rectal cancer treated with preoperative fluorouracil-based chemoradiation

Purpose— Rectal cancer is often clinically resistant to radiotherapy and there would be value to identifying molecular markers to define the biological basis for this phenomenon. NF- κ B is a potentially anti-apoptotic transcription factor that has been associated with resistance to radiotherapy in model systems. This study was designed to evaluate NF- κ B activation in rectal cancers being treated with chemoradiation to determine whether NF- κ B activity correlates with outcome in rectal cancer Methods and Materials— 22 patients were biopsied at multiple time points in a prospective study, and another 50 were analyzed retrospectively. Pre-treatment tumor tissue was analyzed for multiple NF- κ B subunits by immunohistochemistry (IHC). Serial tumor biopsies were analyzed for NF- κ B-regulated gene expression by RT-PCR and for NF- κ B subunit nuclear localization by IHC. Results— Several NF- κ B target genes (Bcl-2, cIAP-2, IL-8 and TRAF1) were significantly upregulated by a single fraction of radiotherapy at 24 hours demonstrating for the first assess the effect of NF- κ B target gene upregulation on response to RT. Our results suggest that NF- κ B may play an important role in tumor metastasis as opposed to resistance to chemoradiotherapy.

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