Review Articles: Colorectal cancerCombination chemoprevention future direction of colorectal cancer preventionZhou, Pinga; Cheng, Shao-Wenb; Yang, Ronga; Wang, Binga; Liu, Jianc Author Information aDepartment of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University bDepartment of Orthopaedic Surgery, the Second Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang cDepartment of Oncology, Hangzhou Chinese Medicine Hospital, Hangzhou, China Correspondence to Dr Liu Jian, PhD, Department of Oncology, Hangzhou Chinese Medicine Hospital, 453 Stadium Road, Hangzhou 310007, Zhejiang Province, China Tel: +8613567114491; fax: +0571 87245618; e-mail: [email protected] Received July 16, 2011 Accepted September 20, 2011 European Journal of Cancer Prevention: May 2012 - Volume 21 - Issue 3 - p 231-240 doi: 10.1097/CEJ.0b013e32834dbbfd Buy Metrics 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. © 2012 Lippincott Williams & Wilkins, Inc.