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

R. Brooks Robey, Judith Weisz, Nancy Kuemmerle, Anna C. Salzberg, Arthur Berg, Dustin G. Brown, Laura Kubik, Roberta Palorini, Fahd Al-Mulla, Rabeah Al-Temaimi, Annamaria Colacci, Chiara Mondello, Jayadev Raju, Jordan Woodrick, A. Ivana Scovassi, Neetu Singh, Monica Vaccari, Rabindra Roy, Stefano Forte, Lorenzo MemeoHosni K. Salem, Amedeo Amedei, Roslida A. Hamid, Graeme P. Williams, Leroy Lowe, Joel Meyer, Francis L. Martin, William H. Bisson, Ferdinando Chiaradonna, Elizabeth P. Ryan

Research output: Contribution to journalReview article

35 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)S203-S231
JournalCarcinogenesis
Volume36
DOIs
StatePublished - Jun 1 2015

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Carcinogenesis
Neoplasms
Toxicology
Gene Expression

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Brooks Robey, R. ; Weisz, Judith ; Kuemmerle, Nancy ; Salzberg, Anna C. ; Berg, Arthur ; Brown, Dustin G. ; Kubik, Laura ; Palorini, Roberta ; Al-Mulla, Fahd ; Al-Temaimi, Rabeah ; Colacci, Annamaria ; Mondello, Chiara ; Raju, Jayadev ; Woodrick, Jordan ; Ivana Scovassi, A. ; Singh, Neetu ; Vaccari, Monica ; Roy, Rabindra ; Forte, Stefano ; Memeo, Lorenzo ; Salem, Hosni K. ; Amedei, Amedeo ; Hamid, Roslida A. ; Williams, Graeme P. ; Lowe, Leroy ; Meyer, Joel ; Martin, Francis L. ; Bisson, William H. ; Chiaradonna, Ferdinando ; Ryan, Elizabeth P. / Metabolic reprogramming and dysregulated metabolism : Cause, consequence and/or enabler of environmental carcinogenesis?. In: Carcinogenesis. 2015 ; Vol. 36. pp. S203-S231.
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title = "Metabolic reprogramming and dysregulated metabolism: Cause, consequence and/or enabler of environmental carcinogenesis?",
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.",
author = "{Brooks Robey}, R. and Judith Weisz and Nancy Kuemmerle and Salzberg, {Anna C.} and Arthur Berg and Brown, {Dustin G.} and Laura Kubik and Roberta Palorini and Fahd Al-Mulla and Rabeah Al-Temaimi and Annamaria Colacci and Chiara Mondello and Jayadev Raju and Jordan Woodrick and {Ivana Scovassi}, A. and Neetu Singh and Monica Vaccari and Rabindra Roy and Stefano Forte and Lorenzo Memeo and Salem, {Hosni K.} and Amedeo Amedei and Hamid, {Roslida A.} and Williams, {Graeme P.} and Leroy Lowe and Joel Meyer and Martin, {Francis L.} and Bisson, {William H.} and Ferdinando Chiaradonna and Ryan, {Elizabeth P.}",
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Brooks Robey, R, Weisz, J, Kuemmerle, N, Salzberg, AC, Berg, A, Brown, DG, Kubik, L, Palorini, R, Al-Mulla, F, Al-Temaimi, R, Colacci, A, Mondello, C, Raju, J, Woodrick, J, Ivana Scovassi, A, Singh, N, Vaccari, M, Roy, R, Forte, S, Memeo, L, Salem, HK, Amedei, A, Hamid, RA, Williams, GP, Lowe, L, Meyer, J, Martin, FL, Bisson, WH, Chiaradonna, F & Ryan, EP 2015, 'Metabolic reprogramming and dysregulated metabolism: Cause, consequence and/or enabler of environmental carcinogenesis?', Carcinogenesis, vol. 36, pp. S203-S231. https://doi.org/10.1093/carcin/bgv037

Metabolic reprogramming and dysregulated metabolism : Cause, consequence and/or enabler of environmental carcinogenesis? / Brooks Robey, R.; Weisz, Judith; Kuemmerle, Nancy; Salzberg, Anna C.; Berg, Arthur; Brown, Dustin G.; Kubik, Laura; Palorini, Roberta; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Colacci, Annamaria; Mondello, Chiara; Raju, Jayadev; Woodrick, Jordan; Ivana Scovassi, A.; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Salem, Hosni K.; Amedei, Amedeo; Hamid, Roslida A.; Williams, Graeme P.; Lowe, Leroy; Meyer, Joel; Martin, Francis L.; Bisson, William H.; Chiaradonna, Ferdinando; Ryan, Elizabeth P.

In: Carcinogenesis, Vol. 36, 01.06.2015, p. S203-S231.

Research output: Contribution to journalReview article

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T2 - Cause, consequence and/or enabler of environmental carcinogenesis?

AU - Brooks Robey, R.

AU - Weisz, Judith

AU - Kuemmerle, Nancy

AU - Salzberg, Anna C.

AU - Berg, Arthur

AU - Brown, Dustin G.

AU - Kubik, Laura

AU - Palorini, Roberta

AU - Al-Mulla, Fahd

AU - Al-Temaimi, Rabeah

AU - Colacci, Annamaria

AU - Mondello, Chiara

AU - Raju, Jayadev

AU - Woodrick, Jordan

AU - Ivana Scovassi, A.

AU - Singh, Neetu

AU - Vaccari, Monica

AU - Roy, Rabindra

AU - Forte, Stefano

AU - Memeo, Lorenzo

AU - Salem, Hosni K.

AU - Amedei, Amedeo

AU - Hamid, Roslida A.

AU - Williams, Graeme P.

AU - Lowe, Leroy

AU - Meyer, Joel

AU - Martin, Francis L.

AU - Bisson, William H.

AU - Chiaradonna, Ferdinando

AU - Ryan, Elizabeth P.

PY - 2015/6/1

Y1 - 2015/6/1

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