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| 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.
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| Citation |
- 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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| Funding Statement (additional comments about funding) |
- The Halifax Project Workshops, held in Halifax, Nova Scotia,
Canada in 2013, received direct support from the United States
National Institute of Environmental Health Sciences. Individual
support is also acknowledged from the United States Department
of Veterans Affairs (to R.B.R.), Fondazione Cariplo (2011-0370 to
C.M.), Rosemere Cancer Foundation (to F.L.M.), Kuwait Institute
for the Advancement of Sciences (2011-1302-06 to F.Al-M.), Grant
University Scheme (RUGs) Ministry Of Education Malaysia (04-02-
12-2099RU to R.A.H.), Italian Ministry of University and Research (2009FZZ4XM_002 to A.A), the University of Florence (ex60%2012
to A.A.), United States Public Health Service (CA92306, CA92306-S1
and CA113447 to R.R.; ES010356 to J.M.), Department of Science
and Technology, Government of India (SR/FT/LS-063/2008 to N.S.),
Associazione Italiana per la Ricerca sul Cancro (IG2014Id.15364 to
F.C.) and SYSBIO and MIUR Fellowships (to R.P.).
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| Additional Information |
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BissonWilliamHEnvironmentalMolecularToxicologyMetabolicReprogrammingDysregulatedSupplementalInfo.pdf: 8089160 bytes, checksum: a929121ec6d40729876887bd61ab8c6d (MD5)
Previous issue date: 2015-06
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