Question ID: Feb 2-2
Submitted by: February 2, 2011 Clinical and Translational Sciences Provocative Questions Workshop - Submitted to the website
March 3, 2011
Can carcinogenesis be prevented or slowed by the long-term use of anti-inflammatory drugs and, if so, by what mechanisms?
Background: Despite a long history of reports of associations between inflammation and carcinogenesis, especially in the colon, anti-inflammatory drugs are not commonly used to mitigate the risk of cancer (largely because of the risk of bleeding associated with non-steroidal anti-inflammatory drugs (NSAIDS), and the mechanism by which inflammation might promote the development of cancers remains poorly understood. A recently published meta-analysis shows that people taking low-dose aspirin to reduce risk of vascular disease have a 20 to 30% lower risk of death due to several types of cancer, including cancers of the esophagus, lung, and pancreas, as well as colon (Lancet, Jan.1, 2011). This study has heightened interest in the relationship of inflammation to carcinogenesis and the potential for use of anti-inflammatory chemoprevention based on a better understanding of the role of inflammation in carcinogenesis.
Feasibility: The cellular and molecular determinants of inflammation can be well characterized by cell fractionation and immunological and biochemical methods. Inflammation can also be observed by imaging techniques. Candidate cell types and molecules could be monitored in long-term prospective clinical trials of anti-inflammatory compounds to determine associations between markers of inflammation and the onset of cancer, and companion analyses with animal models are also feasible. Because aspirin and other NSAIDS are widely used, it is possible to exploit patient records and clinical studies to extend the recently reported findings, as well as to design new studies of the short- and long-term effects of such drugs. Insight might also be obtained from analysis of patients who develop tumors at sites associated with protection by NSAIDS, as such treatment “failures” could be attributable to a class of tumors whose development is intrinsically NSAID-insensitive, to patients who have less suppression of inflammation for a given NSAID dose, or to other factors.
Implications of success: The identification of specific markers of chronic inflammation associated with the development of various cancers would be a major breakthrough in cancer prevention. Determining that there are distinct classes of tumors whose development is or is not influenced by anti-inflammatory agents would provide important insight into the heterogeneity of cancers. Controlling chronic inflammation as measured by specific cellular and molecular markers may provide an intermediate endpoint for the evaluation of cancer chemoprevention and facilitate new approaches to reducing the risk of cancer death with existing or novel anti-inflammatory agents. Success in this endeavor would also encourage the ancillary evaluation of cancer incidence in the context of intervention studies of other widely used drugs, such as statins and anti-hypertensive agents, which are prescribed for non-cancer indications.
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