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The genetic/metabolic transformation concept of carcinogenesis

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Abstract

The carcinogenesis process is poorly understood and subject to varying concepts and views. A rejuvenated interest has arisen regarding the role of altered cellular intermediary metabolism in the development and progression of cancer. As a result, differing views of the implications of altered metabolism in the development of cancer exist. None of the concepts recognize and incorporate the principles of cell metabolism to cell activity, which are applicable to all cells including the carcinogenesis process. This presentation incorporates a novel concept of carcinogenesis that includes a “genetic/metabolic” transformation that encompasses these principles of cell metabolism to cell activity. The intermediary metabolism transformation is essential to provide the bioenergetic/synthetic, growth/proliferation, and migration/invasive events of malignancy. The concept invokes an “oncogenetic transformation” for the development of neoplastic cells from their precursor normal cells; and a required “genetic/metabolic” transformation for facilitation of the development of the neoplastic cells to malignant cells with the manifestation of the malignant process. Such a concept reveals stages and events of carcinogenesis that provide approaches for the identification of biomarkers and for development of therapeutic agents. The presentation discusses the contemporary application of genetics and proteomics to altered cellular metabolism in cancer; and underscores the importance of proper integration of genetics and proteomics with biochemical and metabolic studies, and the consequences of inappropriate studies.

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Acknowledgements

This report and the studies of LCC and RBF cited herein were supported in part by NIH grants CA79903, DK076783, and DK42839.

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Correspondence to Leslie C. Costello.

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Costello, L.C., Franklin, R.B. The genetic/metabolic transformation concept of carcinogenesis. Cancer Metastasis Rev 31, 123–130 (2012). https://doi.org/10.1007/s10555-011-9334-8

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