Direct causes of most individual human cancers will not be identifiable, but there is incontrovertible evidence that certain chemical agents, radiation, and biologic agents contribute to the overall incidence of cancer. A traditional paradigm has classified carcinogenic agents as environmental, lifestyle-related or occupational, but many agents exhibit a complex interplay between all three sources of exposure. A recent paradigm in environmental carcinogenesis-gene-environment interactions, a concept used to describe the complex interplay between individual or population genetics and responses to chemical agents-has also undergone an expansive transformation into a more contemporary understanding of the human “exposome.” The exposome is the cumulative lifelong burden of disease-contributing stressors including exogenous and endogenous agents of all types, as well as an individual’s “omics” profile (genomics, epigenomics, transcriptomics, proteomics, metabolomics), and microbiome. Another traditional model of environmental carcinogenesis, that of the classic sequential model of initiation, promotion, conversion, and progression, has evolved towards less linear models that no longer classify carcinogens as initiators or promoters per se. Instead, we seek to understand the contribution of chemical agents to the various hallmarks of cancer: genomic instability, resisting cell death, deregulating cellular energetics, sustaining proliferative signals, evading growth suppressors, avoiding immune destruction, enabling replicative immortality, promoting tumor inflammation, activating invasion and metastasis, and inducing angiogenesis. These evolving new thought paradigms hold promise for improved exposure monitoring, more accurate identification and earlier detection of disease-consequential exposures, and increasingly effective primary, secondary, and tertiary public health and clinical cancer prevention and interception measures.
- Abeloff’s Clinical Oncology
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International Standard Book Number 13 (ISBN-13)
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