COX2/PTGS2 Expression Is Predictive of Response to Neoadjuvant Celecoxib in HER2-negative Breast Cancer Patients

Crémoux, Patricia de; Hamy, Anne-Sophie; Lehmann-Che, Jacqueline; Scott, Véronique; Sigal, Brigitte; Mathieu, Marie‐Christine; Bertheau, Philippe; Guinebretière, Jean Marc; Pierga, Jean Yves; Giacchetti, Sylvie; Brain, Étienne; Marty, M.; Asselain, Bernard; Spyratos, Frédérique; Bièche, Ivan

doi:10.21873/anticanres.12375

Cited by 9 publications

(7 citation statements)

References 11 publications

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“…Cyclooxygenase-2 (COX-2), the enzyme that catalyzes prostaglandin synthesis, has been extensively investigated as a target in cancer therapy and prevention ( Wang et al, 2005 ; Zha et al, 2001 ; Gupta et al, 2000 ; Yoshimura et al, 2000 ; Krishnan & Feldman, 2010 ; Sun et al, 2018 ). COX-2 is overexpressed in putative cancer precursor inflammatory lesions in tissues such as breast and prostate, in a variety of cancer cell lines, as well as in macrophages and other cells in the tumor microenvironment ( de Cremoux et al, 2018 ; Sano et al, 2018 ). Calcitriol regulates the expression of several genes in the prostaglandin pathway; in vitro and in vivo studies demonstrate that calcitriol + nonsteroidal anti-inflammatory agents which inhibit COX-2 potentiate the growth inhibitory effects of calcitriol ( Davila-Gonzalez et al, 2017 ; Basudhar et al, 2017 ).…”

Section: Anticancer Effects Of Vitamin D Compoundsmentioning

confidence: 99%

Calcitriol and cancer therapy: A missed opportunity

Trump

2018

Bone Reports

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The vitamin D receptor is expressed in most tissues of the body – and the cancers that arise from those tissues. The vitamin D signaling pathway is active in those tissues and cancers. This is at least consistent with the hypothesis that perturbing this signaling may have a favorable effect on the genesis and growth of cancers. Epidemiologic data indicate that vitamin D signaling may be important in the initiation and outcome of a number of types of cancer. Many studies have shown that calcitriol (1,25 dihydroxycholecalciferol) and other vitamin D compounds have antiproliferative, pro-apoptotic, anti-cell migration and antiangiogenic activity in a number of preclinical studies in many different cancer types. Unfortunately, the assessment of the activity of calcitriol or other vitamin D analogues in the treatment of cancer, as single agents or in combination with other anticancer agents has been stymied by the failure to adhere to commonly accepted principles of drug development and clinical trials conduct.

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Section: Anticancer Effects Of Vitamin D Compoundsmentioning

confidence: 99%

Calcitriol and cancer therapy: A missed opportunity

Trump

2018

Bone Reports

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“…COX2 produces prostaglandin-endoperoxide synthase (PTGS) under the regulation of specific stimulus events, such as responding to physiological stress responses, infection, and inflammation. Usually, COX2 and PTGS2 are combined to represent [ 65 , 66 , 67 , 68 ]. In this study, after conducting network-feature topology analysis on the PR candidate compounds–depression targets network, it was found that COX2 and PTGS2 have the same degree value, which is the largest value among the targets.…”

Section: Discussionmentioning

confidence: 99%

Interpreting the Mechanism of Active Ingredients in Polygonati Rhizoma in Treating Depression by Combining Systemic Pharmacology and In Vitro Experiments

Wei,

Wang,

Liu

et al. 2024

Nutrients

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Polygonati Rhizoma (PR) has certain neuroprotective effects as a homology of medicine and food. In this study, systematic pharmacology, molecular docking, and in vitro experiments were integrated to verify the antidepressant active ingredients in PR and their mechanisms. A total of seven compounds in PR were found to be associated with 45 targets of depression. Preliminarily, DFV docking with cyclooxygenase 2 (COX2) showed good affinity. In vitro, DFV inhibited lipopolysaccharide (LPS)-induced inflammation of BV-2 cells, reversed amoeba-like morphological changes, and increased mitochondrial membrane potential. DFV reversed the malondialdehyde (MDA) overexpression and superoxide dismutase (SOD) expression inhibition in LPS-induced BV-2 cells and decreased interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6 mRNA expression levels in a dose-dependent manner. DFV inhibited both mRNA and protein expression levels of COX2 induced by LPS, and the activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) and caspase1 was suppressed, thus exerting an antidepressant effect. This study proves that DFV may be an important component basis for PR to play an antidepressant role.

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“…Combination of celecoxib with other chemotherapies including taxanes have been tested in preclinical models and clinical trials and showed some indication of efficacy ( 73 , 74 ). However, these trials revealed an unmet need for biomarkers to better identify which cancers may respond to combination treatments that include celecoxib ( 75 , 76 ). While downregulation of E-cadherin may not always be necessary for response to celecoxib, our study shows that COX-2 can maintain cell-to-cell adhesions in HR – aggressive BC cells through GSK3β inhibition.…”

Section: Discussionmentioning

confidence: 99%

Stabilization of E-cadherin adhesions by COX-2/GSK3β signaling is a targetable pathway in metastatic breast cancer

Balamurugan¹,

Poria²,

Sehareen³

et al. 2023

JCI Insight

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COX2/PTGS2 Expression Is Predictive of Response to Neoadjuvant Celecoxib in HER2-negative Breast Cancer Patients

Abstract: COX2 overexpression is predictive of pCR in patients with celecoxib-treated tumors. The efficacy of celecoxib in breast cancer might be improved by quantification of COX2 gene expression.

Cited by 9 publications

References 11 publications

Calcitriol and cancer therapy: A missed opportunity

Calcitriol and cancer therapy: A missed opportunity

Interpreting the Mechanism of Active Ingredients in Polygonati Rhizoma in Treating Depression by Combining Systemic Pharmacology and In Vitro Experiments

Stabilization of E-cadherin adhesions by COX-2/GSK3β signaling is a targetable pathway in metastatic breast cancer

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