ReviewInflammation: Gearing the journey to cancer
Section snippets
Chronic inflammation as a predisposing factor for malignant transformation of cells
Chronic inflammation represents a major pathologic basis for the majority of human malignancies. The role of inflammation in carcinogenesis has first been proposed by Rudolf Virchow in 1863, when he noticed the presence of leukocytes in neoplastic tissues [1]. Since the Virchow's early observation that linked inflammation and cancer, accumulating data have supported that tumors can originate at the sites of infection or chronic inflammation [2]. Approximately, 25% of all cancers are somehow
Major mediators linking inflammation and cancer
Chronic inflammation is implicated in all stages of carcinogenesis, i.e., initiation, promotion and progression. In a persistently inflamed tissue, excessive generation of ROS can cause genomic instability which leads to initiation of cancer [3], [61]. A single initiated cell undergoes proliferation to produce a clone of mutated cells which form premalignant mass, the event generally termed tumor promotion. Some of the preneoplastic cells encounter additional mutations and become malignant.
Inflammatory angiogenesis in cancer
The role of inflammation in angiogenesis has been evolutionarily recognized in physiological processes, such as development of uterine and intestinal vasculature [206]. Angiogenesis is also essential for the growth and survival of solid tumors, and their progression to invasive phenotypes. The concept of angiogenesis as a mechanism of growth and survival of tumor cells was first introduced by Folkman et al., who proposed that tumor cells could sense their distance from the normal vasculature
Role of miRNA in cancer
In the field of epigenetics, microRNAs (miRNAs or miR) have emerged as a novel class of gene expression regulators. The miRNAs constitute a large family of non-coding-, small size- (19–22 oligonucleotides), and gene-silencing RNAs, which negatively regulate gene expression via translational repression and/or mRNA degradation. miRNAs are transcribed by RNA polymerase II forming a long primary transcript (pri-miRNA), which is processed into a short hairpin structure (pre-miRNA) by nuclear RNase
Components of inflammatory signaling cascades as targets for chemoprevention
Chemoprevention is a practical approach of preventing cancer by using relatively non-toxic chemical entities to halt, reverse or delay the carcinogenic process [119]. One of the promising strategies for chemoprevention is to alleviate inflammatory responses, which is implicated in all stages of tumorigenesis [255]. Numerous synthetic and natural compounds with anti-inflammatory properties have been identified as attractive chemopreventive arsenal [119], [255]. At the molecular level, the
Conclusion
Despite enormous effort to conquer cancesur over the last few decades, the outcome of conventional strategies, such as chemotherapy and radiotherapy, to combat cancer appears unsatisfactory as the incidence and the mortality of cancer, in general, are not decreasing worldwide. The concept of chemoprevention, therefore, appears to be a realistic and fundamental approach to fight cancer. Illuminating an inflammation-cancer link corroborates that chemoprevention can be achieved, partly, by
Acknowledgements
This work was supported by the grants for 21C Frontier Functional Human Genome Project (grant number FG07-21-21), the Innovative Drug Research Center (grant number: R11-2007-107-0000-0) and the National Research Laboratory from Korea Science and Engineering Foundation, from the Ministry of Science and Technology, Republic of Korea. Joydeb Kumar Kundu is a recipient of Brain Korea-21 (BK-21) post-doctoral fellowship.
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On leave from Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh.