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Epidemiology and molecular pathology at crossroads to establish causation: molecular mechanisms of malignant transformation

Oncogene volume 23, pages 6484–6491 (2004)Cite this article

Abstract

Epidemiology is a very reliable science for the identification of carcinogens. Epidemiological studies require that the effect, cancer in this case, has already occurred, when of course it would be more desirable to identify potential carcinogenic substances at an earlier stage before they have caused a large number of malignancies and thus become identifiable by epidemiological studies. In the past 30 years, molecular pathology (which includes chemistry, biochemistry, molecular biology, molecular virology, molecular genetics, epigenetics, genomics, proteomics, and other molecular-based approaches) has identified some key alterations that are required for cellular transformation and malignancy. Agents that specifically interfere with some of these mechanisms are suspected human carcinogens. It can be stated that tumor formation requires the following steps: (1) inactivation of Rb and p53 cellular pathways; (2) activation of Ras and/or other growth promoting pathways; (3) inactivation of phosphatase 2A that causes changes in the phosphorylation and activity of several cellular proteins; (4) evasion of apoptosis; (5) telomerase activation or alternative mechanisms of cellular immortalization; (6) angiogenic activity; and (7) the ability to invade surrounding tissues and to metastasize. Here, we review the molecular mechanisms of cellular transformation. The integration of this knowledge with classical epidemiology and animal studies should permit a more rapid and accurate identification of human carcinogens.

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Acknowledgements

Dr Carbone's work is supported by grants from the National Cancer Institute, USA, RO1CA92657; the American Cancer Society, RSG-04-029-01-CCE, and by the Cancer Research Foundation of America.

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  1. Cardinal Bernardin Cancer Center, Loyola University Chicago, 2160 South First Ave, Maywood, 60153, IL, USA

    Maurizio Bocchetta & Michele Carbone

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  1. Maurizio Bocchetta
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  2. Michele Carbone
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Correspondence to Maurizio Bocchetta.

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Bocchetta, M., Carbone, M. Epidemiology and molecular pathology at crossroads to establish causation: molecular mechanisms of malignant transformation. Oncogene 23, 6484–6491 (2004). https://doi.org/10.1038/sj.onc.1207855

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