title: Combination chemoprevention:  future direction of colorectal cancer prevention.
abstract: Recent research has drawn attention to protective effects of chemopreventive agents that reverse, suppress, or prevent the carcinogenic progression using pharmacological or nutritional agents. Aspirin and celecoxib are the promising preventive agents to effectively reduce the risk of colorectal cancer, but such agents are associated with severe gastrointestinal and cardiovascular side effects in long-term administration at high doses. Recently, the strategy that combinational use with several chemopreventive agents at low doses induces greater inhibition of carcinogenesis has become the focus. The nonsteroidal anti-inflammatory drugs (NSAIDs) may combine with ornithine decarboxylase inhibitors, hydroxymethylglutaryl-CoA reductase inhibitors, epidermal growth factor signaling inhibitors, peroxisome proliferator-activated receptor-γ ligands, and tumor necrosis factor-related apoptosis-inducing ligand, to magnify the chemoprophylactic effect. It is noteworthy that the phase III trial of difluoromethylornithine combination with sulidac has shown greater and effective preventive roles, which pave the way for the use of combinations of other agents. The long-term statins and low-dose NSAIDs have also been associated with risk reduction in vitro, in vivo, and in retrospective studies; however, the data are inconsistent. Epidermal growth factor signaling inhibitors, peroxisome proliferator-activated receptor-γ ligands and tumor necrosis factor-related apoptosis-inducing ligand have been demonstrated to potentiate the preventive effects of NSAIDs in vitro and in vivo, but these combinational regimens have not yet been applied to clinical research. The major goal of this study was to review combination chemoprevention for colorectal cancer by means of combining low doses of potential preventive agents to increase their chemoprophylaxis efficacy and to minimize toxicity.
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Wenzhou, Zhejiang, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.forename: Shao-Wen
authors.initials: SW
authors.lastname: Cheng
authors.forename: Rong
authors.initials: R
authors.lastname: Yang
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000517:prevention & control*; D000518:Eflornithine / Q000627:therapeutic use; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D005544:Forecasting; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D047495:PPAR gamma / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D047495:PPAR gamma; D053221:TNF-Related Apoptosis-Inducing Ligand; D066246:ErbB Receptors; D000518:Eflornithine