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Metabolic reprogramming and dysregulated metabolism: cause, consequence and/or enabler of environmental carcinogenesis?

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Title Metabolic reprogramming and dysregulated metabolism: cause, consequence and/or enabler of environmental carcinogenesis?
Names Robey, R. Brroks (creator)
Weisz, Judith (creator)
Kuemmerle, Nancy (creator)
Bisson, William H. (creator)
et al. (creator)
Date Issued 2015-06 (iso8601)
Note This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Oxford University Press. The published article can be found at: http://carcin.oxfordjournals.org/
Abstract Environmental contributions to cancer development are widely accepted, but only a fraction of all pertinent exposures
have probably been identified. Traditional toxicological approaches to the problem have largely focused on the effects of
individual agents at singular endpoints. As such, they have incompletely addressed both the pro-carcinogenic contributions
of environmentally relevant low-dose chemical mixtures and the fact that exposures can influence multiple cancer-associated endpoints over varying timescales. Of these endpoints, dysregulated metabolism is one of the most common
and recognizable features of cancer, but its specific roles in exposure-associated cancer development remain poorly
understood. Most studies have focused on discrete aspects of cancer metabolism and have incompletely considered both
its dynamic integrated nature and the complex controlling influences of substrate availability, external trophic signals
and environmental conditions. Emerging high throughput approaches to environmental risk assessment also do not
directly address the metabolic causes or consequences of changes in gene expression. As such, there is a compelling
need to establish common or complementary frameworks for further exploration that experimentally and conceptually
consider the gestalt of cancer metabolism and its causal relationships to both carcinogenesis and the development of
other cancer hallmarks. A literature review to identify environmentally relevant exposures unambiguously linked to both
cancer development and dysregulated metabolism suggests major gaps in our understanding of exposure-associated
carcinogenesis and metabolic reprogramming. Although limited evidence exists to support primary causal roles for
metabolism in carcinogenesis, the universality of altered cancer metabolism underscores its fundamental biological
importance, and multiple pleiomorphic, even dichotomous, roles for metabolism in promoting, antagonizing or otherwise
enabling the development and selection of cancer are suggested.
Genre Article
Identifier Robey, R. B., Weisz, J., Kuemmerle, N., Salzberg, A. C., Berg, A., Brown, D. G., ... & Ryan, E. P. (2015). Metabolic reprogramming and dysregulated metabolism: cause, consequence and/or enabler of environmental carcinogenesis?. Carcinogenesis, 36(Suppl 1), S203-S231. doi:10.1093/carcin/bgv037

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