The discovery and development of cyclooxygenase-2 inhibitors as potential anticancer therapies

Abstract

There have been a number of PTGS2 (COX-2) selective inhibitors suggested as potential anticancer therapies. In recent years, the development of nanotechnology has also had an impact on chemotherapy. Indeed, nanoparticles of cytotoxic drug carriers have demonstrated potential through their accumulation in cancer cells, and targeting these nanoparticles has been under evaluation. This area could be opened up for coxib development as they are potentially important targets in cancer cells. Further research using celecoxib as a co-drug with PTGS2-overexpressed and PTGS2-independent cancer is still needed.

Resistance of cyclooxygenase-2 expressing pancreatic ductal adenocarcinoma cells against γδ T cell cytotoxicity

“…14,15,43,44 However, the application of Celecoxib over a prolonged period of time seems to be critical since it may cause cardiovascular side effects. 12 Moreover, the effect of Celecoxib alone induced different effects on pancreatic cancer cells. 12,45 In our experiments, we used different Cox inhibitors, which did not induce cell death or cell cycle arrest in PDAC cells in the used concentrations but inhibited the PGE2 release.…”

“…12 Moreover, the effect of Celecoxib alone induced different effects on pancreatic cancer cells. 12,45 In our experiments, we used different Cox inhibitors, which did not induce cell death or cell cycle arrest in PDAC cells in the used concentrations but inhibited the PGE2 release. Our data demonstrate that a combined immunotherapy with Cox-2 inhibitors together with the newly designed tribody [(Her2) 2 £Vg9] gives us a tool to efficiently induce the gd T cell-mediated lysis of Colo357 PDAC cells.…”

“…11 Although selective Cox-2 inhibitors such as celecoxib and DuP697 showed anti-proliferative activity toward different tumor entities and against several PDAC cell lines in vitro as well as in vivo, celecoxib as a single agent failed to exert anti-proliferative or antitumor effects toward pancreatic adenocarcinomas resected from patients and implanted in nude mice in a xenograft model, despite a decrease in PGE2 synthesis. [11][12][13] Nevertheless, selective Cox-2 inhibitors have been included in clinical trials (Phase II) as combinatorial therapies, such as to increase the efficiency of the topoisomerase I inhibitor irinotecan or chemotherapy for the treatment of patients with advanced or metastatic pancreatic adenocarcinoma. 12,14,15 PDAC is a highly malignant gastrointestinal tumor characterized by the presence of a dense desmoplastic stroma composed of extracellular matrix and diverse non-neoplastic inflammatory cells mostly displaying an immunosuppressive phenotype.…”

“…[11][12][13] Nevertheless, selective Cox-2 inhibitors have been included in clinical trials (Phase II) as combinatorial therapies, such as to increase the efficiency of the topoisomerase I inhibitor irinotecan or chemotherapy for the treatment of patients with advanced or metastatic pancreatic adenocarcinoma. 12,14,15 PDAC is a highly malignant gastrointestinal tumor characterized by the presence of a dense desmoplastic stroma composed of extracellular matrix and diverse non-neoplastic inflammatory cells mostly displaying an immunosuppressive phenotype. The overall 5-year survival rate is less than 5%.…”

COX-2 Inhibitors, a Potential Synergistic Effect with Antineoplastic Drugs in Lung Cancer

“…In addition, selective COX-2 inhibitors such as celecoxib have been included in clinical trials in non-small-cell lung cancer patients showing promising results [26][27][28]. Moreover, results from another clinical trial in adenoma cancer patients showed significant benefit effect in the celecoxib group of patients [29].…”