Intratumoral COX-2 Gene Expression Is a Predictive Factor for Colorectal Cancer Response to Fluoropyrimidine-Based Chemotherapy

Abstract

Purpose: Cyclooxygenase-2 (COX-2) is generally elevated in tumors compared with normal tissue and apparently has an important role in tumor development. A number of studies have found high expression of COX-2 to be an unfavorable prognostic factor for overall survival in several cancers. However, the influence of COX-2 expression levels on tumor response to chemotherapy has been relatively little studied. The purpose of this study was to ascertain if COX-2 gene expression is associated with tumor response in the clinical treatment of colorectal cancer with the fluoropyrimidine-based therapy S-1. 2 , 120 mg/d) for 28 days followed by a 2-week period rest. mRNA was isolated from paraffin-embedded pretreatment primary tumor specimens and expression levels of COX-2 relative to b-actin as the internal reference gene were measured using a quantitative reverse transcription-PCR (Taqman) system. Results: The overall response rate in a group of 44 patients treated with S-1was 40.9%. Sufficient tumor tissue was available from 40 of these patients for COX-2 mRNA quantitation. COX-2 gene expression was significantly lower in the responding tumors compared with the nonresponders (P = 0.012,Wilcoxon test). Patients with COX-2 values above the cutoff value of 3.28 Â 10 À3 had a significantly shorter survival than those with COX-2 gene expressions below the cutoff value (adjusted P = 0.031). Conclusions: Intratumoral COX-2 gene expression is associated with likelihood of response to chemotherapy with S-1 and is a prognostic factor for survival of patients after the start of S-1 chemotherapy.

COX-2 promotes metastasis in nasopharyngeal carcinoma by mediating interactions between cancer cells and myeloid-derived suppressor cells

“…[30][31][32] Here, the expression level of COX-2 was significantly higher in tumor biopsies compared with tumoradjacent tissues from 26 paired NPC patients (P < 0.05, n D 26), as shown in Fig. 1A.…”

Serial Changes in Expression of Proteins in Response to Neoadjuvant Chemotherapy in Breast Cancer

“…This is based on the premise that many of the COX-2-regulated genes that contribute to tumour progression may also be determinants of tumour sensitivity to treatment (137). Although the potential chemopreventive properties of selective COX-2 inhibitors are being actively investigated, little is known about the utility of these agents in the treatment of cancer.…”

“…Although the potential chemopreventive properties of selective COX-2 inhibitors are being actively investigated, little is known about the utility of these agents in the treatment of cancer. However, there is emerging data from breast, pancreatic and lung cancer studies showing potential benefit of combining COX-2 inhibitors with chemotherapy (137)(138)(139). In particular, a recent study involving patients with heavily pretreated breast cancer showed that the combination of chemotherapy and a selective COX-2 inhibitor resulted in a statistically significant doubling of time to progression for COX-2-positive tumours compared with COX-2 negative ones.…”

Polarized dendritic cells as cancer vaccines: Directing effector-type T cells to tumors

“…DCs present in patients with advanced cancer are a target of tumor-associated suppressive factors, resulting in their suppressed ability to support effector functions in tumor-specific lymphocytes (41,42). Known mediators of DC dysfunction include IL-10, TGF-β, VEGF, IL-6, and COX2 products, particularly PGE 2 (43–47). DCs that develop in their presence show impaired maturation and reduced expression of costimulatory molecules needed to support T cell activation, and suppressed production of cytokines needed to support survival and anti-tumor effector functions of tumor-specific T cells (5,48–51).…”