Inflammation and cancer: how friendly is the relationship for cancer patients?
Introduction
Cancer is one disease that fits the paradigm that “more we know, less we understand its intricacies”. That continuous irritation over long periods of time can lead to cancer, has been described in Ayurveda (means the science of long life), written as far back as 5000 years ago. Whether this irritation is the same as that Rudolf Virchow referred to as inflammation in the nineteenth century is uncertain. The observable consequences of irritation were first described by Aulus Cornelius Celsus, a Roman medical writer and possibly a physician in the first century (ca. 25 BC–50 AD), who characterized inflammation as “redness (rubor) and swelling (tumor) with heat (calor) and pain (dolor)”. Virchow postulated that microinflammation that results from irritation leads to the development of most chronic diseases including cancer. This inflammation is now regarded as a “secret killer” for diseases such as atherosclerosis, rheumatoid arthritis, multiple sclerosis, asthma, Alzheimer's, depression, fatigue, neuropathic pain, lack of appetite, and cancer [1]. With the recent advent of molecular biology, cell signaling, recombinant DNA, and genomics, there has been reawakening and tremendous interest in the role of inflammation in cancer and other diseases. This review will focus primarily on the role of inflammation in cancer.
Section snippets
Inflammatory network in cancer
In the past two decades numerous molecules have been identified that play a critical role in inflammation. These include tumor necrosis factor (TNF), interleukin-1 (IL-1), interleukin-6 (IL-6), chemokines, cyclooxygenase (COX)-2, 5 lipooxygenase (LOX), matrix metalloproteases (MMP), vascular endothelial growth factor (VEGF), TWIST and cell surface adhesion molecules. What is common to all these molecules is that they are regulated by the transcription factor NF-κB (Figure 1). Although initially
Evidence that inflammatory genes/products are overexpressed in cancer patients
Both TNF and NF-κB, two major mediators of inflammation (isolated around 1984 and 1986, respectively) are now the subjects of around 73,000 and 27,000 citations respectively. The Pubmed database also shows 2300 citation for NF-κB in patients in general and around 800 in cancer patients alone. Thus it is not possible to cover all the information.
Both NF-κB and NF-κB gene products have been, however, linked with prognosis and response to therapy in patients with different cancers (see Table 1,
Inhibitors of inflammation in the clinic for treatment of cancer patients
From these studies, it is clear that various inflammatory markers are expressed in various cancers and they mediate progression of the diseases. Thus agents which suppress these inflammatory markers or the pathways activated by them have a potential for prevention and treatment of cancer (Figure 3). Some of the agents that have potential to suppress these pathways and are being tested include steroids (such as dexamethasone and predensilon), proteasome inhibitors (such as velcade), TNF
Conclusion
All the studies described above provide conclusive proof that inflammation is a critical mediator of cancer. Thus antinflammatory agents should be explored for both prevention and treatment of cancer. Although numerous cell culture and animal studies have identified several natural anti-inflammatory agents, their true potential will be recognized only through well-controlled clinical trials. Such studies are urgently needed. Curcumin, a component of turmeric, is one such agent that has been
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgments
We thank Walter Pagel for carefully proofreading the manuscript and providing valuable comments. Dr. Aggarwal is the Ransom Horne, Jr., Professor of Cancer Research. This work was supported by a grant from the Clayton Foundation for Research (B.B.A.), a core grant from the National Institutes of Health (CA-16 672), a program project grant from National Institutes of Health (NIH CA-124787-01A2), and a grant from Center for Targeted Therapy of M.D. Anderson Cancer Center.
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