Overview of cancer

The sequence of events from mutations or damage to proto-oncogenes and leads to tumour suppressor genes, loss of development of cancer, with its metabolic disturbances and cachexia. Finally these changes can lead to 

Infection with a retroviras is the most common way in which viruses cause cancer (see above). The first work that led to the discovery that a virus could cause cancer was that of Dennis Burkitt which was published in 1958 (Box 21.1). As 

Sites of cancer Major established factors Minor estabUshed risk factors Other possible factors 

Breast r Early menarche Postmenopausal obesity 1 Steroid hormones 

Bladder Smoking Aromatic amines Oral contraceptives 

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Davis ID. An overview of cancer immunotherapy. Immunol Cell Biol 2000 78(3) 179-195. 

Lim G. C. C.(2002) Overview of Cancer in Malaysia, In Japanese Journal of Clinical Oncology, Department of Radiotherapy and Oncology, Hospital Kuala Lumpur,2002... 

Lage, H. (2008). An overview of cancer multidrug resistance a still unsolved problem. Cell Mol. Life Sci. 65, 3145-3167. 

Aapro MS 5-HT3 receptor antagonists an overview of their present status and future potential in cancer therapy-induced emesis. Drugs 42 551-568, 1991... 

Archer, V.J., Oncology Overview, Selected Abstracts on Risk of Cancer from Exposure to Low Level Ionizing Radiation, PB84-922906, International Cancer Research Data Bank Program, National Cancer Institute, U.S. Department of Health and Human Services, Salt Lake City, Utah, (August 1984) ... 

It is remarkable that most of the data collected from the available SERMs are unanimous in reproducing an estrogen agonistic profile in venous thrombogenesis. The vast clinical experience acquired with tamoxifen confirms an augmented risk for both deep venous thrombosis and pulmonary embolism. This increase, however, did not presuppose increased mortality in the overview of randomized trials of adjuvant tamoxifen for early breast cancer, where the one extra death per 5000 woman-years of tamoxifen attributed to pulmonary embolus was not statistically significant (Early Breast Cancer Trialists Collaborative Group 1998). 

Early Breast Cancer Trialists Collaborative Group (1998) Tamoxifen for early breast cancer an overview of the randomised trials. Lancet 351 1451-1467... 

Cuzick J, Powles T, Veronesi U et al. (2003) Overview of the main outcomes in breast-cancer prevention trials. Lancet 361(9354) 296-300... 

Cachexia accompanies many diseases, which include sepsis, diabetes and AIDS, as weU as cancer (Chapter 16). The metabolic changes in cachexia are an extension of those presented above, but are more severe. An overview of the metabolic changes in cancer is given in Figure 21.24. The metabolic changes that occur in patients, after trauma and during cancer can be compared by reference to Table 21.5. 

Figure 21.24 An overview of amino acid metabolism, particularly amino acid metabolism, in a patient suffering from cancer. The tumour acts as a sink for glucose, amino acids and glutamine. As tumour grows in size, the sink is exaggerated and cachexia develops. This diagram can be considered with that in Figure 21.22 in order to include fatty acids in tumour metabolism. Note the thicker line to indicate magnitude of release of glutamine by muscle.

Many sites of exposure to bile in the body are associated with the development of cancer, e.g. the oesophagus, gallbladder and bile duct, pancreas, small intestine and colon (reviewed in ref. 2). One explanation for increased cancer at these sites could be that bile acids stimulate carcinogenesis via DNA-damaging effects. This chapter provides an overview of research conducted in relation to establishing the genotoxic and carcinogenic effects of bile acids. 

The quantitative dose-response assessment involves two different challenges, namely to determine the relationship between doses and the frequency of cases of cancer (i.e., potency evaluation), and to determine what statistical risk is tolerable or acceptable. This section gives a very short overview of some general aspects related to the quantitative dose-response assessment. The currently used approach by the WHO, the US-EPA, and the EU, as well as new approaches for the risk assessment of compounds that are both genotoxic and carcinogenic, are presented in Sections 6.3 and 6.4, respectively. 

The following overview of the US-EPA revised quantitative approach for cancer risk assessment is based on the final version of the Guidelines for Carcinogen Risk Assessment (US-EPA 2005). 

In summary, due fo fhe large panel of cell cycle regulatory proteins regulated by HDACs at the level of either their expression or activity, the antiproliferative effect of HDAC inhibitors cannot be linked to a single mechanism of action. The relative importance of the different proteins affected by HDACs varies between tumors. In Fig. 2, a visual overview of the role of HDACs in various hallmark processes in the development of cancer is shown. 

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