Inflammation & Cancer

Inflammation (Latin- inflamatio, to set on fire) is the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. As we all know that it is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. But sometimes this inflammatory process can lead to many life-threatening diseases like cardiovascular diseases, inflammatory and autoimmune disorders, neurodegenerative conditions, and cancer.

Tumour has been linked with inflammation since 1863, when Rudolf Virchow discovered leucocytes in neoplastic tissues and made the first connection between inflammation and cancer. Since then, chronic inflammation has been identified as a risk factor for cancer and even as a means to prognose/diagnose cancer at the onset of the disease. Examples of such association include the Human papiloma virus (HPV) and cancer, including cervical , cancers of the oesophagus and larynx, Helicobacter pylori bacterial infection and gastric adenocarcinoma, the hepatitis B virus, cirrhosis and hepato-cellular carcinoma, Schistosoma haematobium and cancer of the bladder, asbestos induced inflammation and bronchogenic carcinoma or mesothelioma in humans.

Several reports implicate inflammation as a significant risk factor in cancer development: asbestos, cigarette smoke and inflammation of the bowel and pancreas are but a few well-known examples given.

How inflammation helps in cancer progression?

1. The inflammation environment is one that would support tumour development and is consistent with that observed in tumour sites.

2. chronic inflammation occurs due to tumour environment stress and that this would generate a protective shield from the immune system.

3. It has been recently demonstrated that the tumour microenvironment highly resembles an inflammation site, with significant advantages for the progression of tumour, including the use of cytokines, chemokines, leucocytes, lymphocytes and macrophages to contribute to both vassal dilation and neovascularisation for increased blood flow, the immunosuppression associated with the malignant disease, and tumour metastasis.

4. Cancer up-regulates the angiotensin II type 1 (AT1) receptor through systemic oxidative stress and hypoxia mechanisms, thereby triggering chronic inflammatory processes to remodel surrounding tissue and subdue the immune system.

5. A gene called I-kappa-B kinase (IKK beta), a pro-inflammatory gene, acts differently in two cell types to cause cancer. When IKK beta was deleted, the cancer incidence and tumor growth in mice was decreased by nearly 80 percent.

Furthermore, this inflammation-site tumour-generated microenvironment, apart from its significant role in cancer progression and protection from the immune system, has a considerable adverse effect to the success of the various current cancer treatments. It has recently been demonstrated that the inflammatory response in cancer can greatly affect the disposition and compromise the pharmacodynamics of chemotherapeutic agents.

References:

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· Munger K: The role of human papillomaviruses in human cancers. Frontiers in Bioscience 2002, 7:D641-D649.

· Castle PE, Hillier S, Rabe L, Hildesheim A, Herrero R, Bratti M, Sherman M, Burk R, Rodriguez A, Alfaro M, Hutchinson M, Morales J, Schiffman M: An Association of Cervical Inflammation with High-Grade Cervical Neoplasia in Women Infected with Oncogenic Human Papillomavirus (HPV). Cancer Epidemiol Biomarkers Prev 2001, 10:1021-1027.

· Syrjanen KJ: HPV infections and oesophageal cancer. Journal of Clinical Pathology 2002, 55:721-728.

· Aaltonen LM, Rihkanen H, Vaheri A: Human papillomavirus in larynx. Laryngoscope 2002, 112(4):700-707

· Naumann M, Crabtree J: Helicobacter pylori-induced epithelial cell signalling in gastric carcinogenesis.Trends in Microbiology 2002, 12:29-36.

· Hilleman M: Critical overview and outlook: pathogenesis, prevention, and treatment of hepatitis and hepatocarcinoma caused by hepatitis B virus. Vaccine 2003, 21:4626-4649.

· Rosin MP, Anwar WA, Ward AJ: Inflammation, chromosomal instability and cancer: the schistosomiasis model. Cancer Res 1994, 54(7 Suppl):1929S-1933S.

· Manninga C, Vallyathanb V, Mossman B: Diseases caused by asbestos: mechanisms of injury and disease development. International Immunopharmacology 2002, 2:191-200.

· Farrow B, Evers BM: Inflammation and the development of pancreatic cancer. Surgical Oncology 2002, 10:153-169.

· Schwartsburd PM: Chronic inflammation as inductor of pro-cancer microenvironment: Pathogenesis of dysregulated feedback control. Cancer and Metastasis reviews 2003, 22:95-102.

· Slaviero KA, Clarke SJ, Rivory LP: Inflammatory response: an unrecognised source of variability in the pharmacokinetics and pharmacodynamics of cancer chemotherapy. Lancet Oncol 2003, 4:224-32.