The Key Characteristics of Carcinogens: Relationship to the Hallmarks of Cancer, Relevant Biomarkers, and Assays to Measure Them

Martyn T Smith; Kathryn Z Guyton; Nicole Kleinstreuer; Alexandre Borrel; Andres Cardenas; Weihsueh A Chiu; Dean W Felsher; Catherine F Gibbons; William H Goodson; Keith A Houck; Agnes Kane; Michele A La Merrill; Herve Lebrec; Leroy Lowe; Cliona M McHale; Sheroy Minocherhomji; Linda Rieswijk; Martha S Sandy; Hideko Sone; Amy Wang; Luoping Zhang; Lauren Zeise; Mark Fielden

doi:10.1158/1055-9965.epi-19-1346

The Key Characteristics of Carcinogens: Relationship to the Hallmarks of Cancer, Relevant Biomarkers, and Assays to Measure Them

Martyn T Smith^*, Kathryn Z Guyton, Nicole Kleinstreuer, Alexandre Borrel, Andres Cardenas, Weihsueh A Chiu, Dean W Felsher, Catherine F Gibbons, William H Goodson, Keith A Houck, Agnes Kane, Michele A La Merrill, Herve Lebrec, Leroy Lowe, Cliona M McHale, Sheroy Minocherhomji, Linda Rieswijk, Martha S Sandy, Hideko Sone, Amy WangLuoping Zhang, Lauren Zeise, Mark Fielden

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

BACKGROUND: The key characteristics (KCs) of human carcinogens provide a uniform approach to evaluating mechanistic evidence in cancer hazard identification. Refinements to the approach were requested by organizations and individuals applying the KCs.

METHODS: We assembled an expert committee with knowledge of carcinogenesis and experience in applying the KCs in cancer hazard identification. We leveraged this expertise and an examination of the literature to more clearly describe each KC; identify current and emerging assays and in vivo biomarkers that can be used to measure them; and, make recommendations for future assay development.

RESULTS: We found that the KCs are clearly distinct from the Hallmarks of Cancer, that interrelationships among the KCs can be leveraged to strengthen the KC approach (and an understanding of environmental carcinogenesis), and that the KC approach is applicable to the systematic evaluation of a broad range of potential cancer hazards in vivo and in vitro. We identified gaps in coverage of the KCs by current assays.

CONCLUSION: Future efforts should expand the breadth, specificity and sensitivity of validated assays and biomarkers that can measure the 10 KCs.

IMPACT: Refinement of the KC approach will enhance and accelerate carcinogen identification, a first step in cancer prevention.

Original language	English
Pages (from-to)	1887-1903
Number of pages	17
Journal	Cancer Epidemiology Biomarkers & Prevention
Volume	29
Issue number	10
Early online date	9 Mar 2020
DOIs	https://doi.org/10.1158/1055-9965.epi-19-1346
Publication status	Published - Oct 2020

Keywords

ARYL-HYDROCARBON RECEPTOR
IN-SILICO PREDICTION
GENOMIC INSTABILITY
REPLICATION STRESS
OXIDATIVE STRESS
BREAST-CANCER
DNA-DAMAGE
INFLAMMATORY BIOMARKERS
CHROMOSOMAL-ABERRATIONS
REACTIVE METABOLITES

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10.1158/1055-9965.epi-19-1346

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Cite this

Smith, M. T., Guyton, K. Z., Kleinstreuer, N., Borrel, A., Cardenas, A., Chiu, W. A., Felsher, D. W., Gibbons, C. F., Goodson, W. H., Houck, K. A., Kane, A., La Merrill, M. A., Lebrec, H., Lowe, L., McHale, C. M., Minocherhomji, S., Rieswijk, L., Sandy, M. S., Sone, H., ... Fielden, M. (2020). The Key Characteristics of Carcinogens: Relationship to the Hallmarks of Cancer, Relevant Biomarkers, and Assays to Measure Them. Cancer Epidemiology Biomarkers & Prevention, 29(10), 1887-1903. https://doi.org/10.1158/1055-9965.epi-19-1346

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title = "The Key Characteristics of Carcinogens: Relationship to the Hallmarks of Cancer, Relevant Biomarkers, and Assays to Measure Them",

abstract = "BACKGROUND: The key characteristics (KCs) of human carcinogens provide a uniform approach to evaluating mechanistic evidence in cancer hazard identification. Refinements to the approach were requested by organizations and individuals applying the KCs.METHODS: We assembled an expert committee with knowledge of carcinogenesis and experience in applying the KCs in cancer hazard identification. We leveraged this expertise and an examination of the literature to more clearly describe each KC; identify current and emerging assays and in vivo biomarkers that can be used to measure them; and, make recommendations for future assay development.RESULTS: We found that the KCs are clearly distinct from the Hallmarks of Cancer, that interrelationships among the KCs can be leveraged to strengthen the KC approach (and an understanding of environmental carcinogenesis), and that the KC approach is applicable to the systematic evaluation of a broad range of potential cancer hazards in vivo and in vitro. We identified gaps in coverage of the KCs by current assays.CONCLUSION: Future efforts should expand the breadth, specificity and sensitivity of validated assays and biomarkers that can measure the 10 KCs.IMPACT: Refinement of the KC approach will enhance and accelerate carcinogen identification, a first step in cancer prevention.",

keywords = "ARYL-HYDROCARBON RECEPTOR, IN-SILICO PREDICTION, GENOMIC INSTABILITY, REPLICATION STRESS, OXIDATIVE STRESS, BREAST-CANCER, DNA-DAMAGE, INFLAMMATORY BIOMARKERS, CHROMOSOMAL-ABERRATIONS, REACTIVE METABOLITES",

author = "Smith, {Martyn T} and Guyton, {Kathryn Z} and Nicole Kleinstreuer and Alexandre Borrel and Andres Cardenas and Chiu, {Weihsueh A} and Felsher, {Dean W} and Gibbons, {Catherine F} and Goodson, {William H} and Houck, {Keith A} and Agnes Kane and {La Merrill}, {Michele A} and Herve Lebrec and Leroy Lowe and McHale, {Cliona M} and Sheroy Minocherhomji and Linda Rieswijk and Sandy, {Martha S} and Hideko Sone and Amy Wang and Luoping Zhang and Lauren Zeise and Mark Fielden",

note = "Copyright {\textcopyright}2020, American Association for Cancer Research.",

year = "2020",

month = oct,

doi = "10.1158/1055-9965.epi-19-1346",

language = "English",

volume = "29",

pages = "1887--1903",

journal = "Cancer Epidemiology Biomarkers & Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research Inc.",

number = "10",

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Smith, MT, Guyton, KZ, Kleinstreuer, N, Borrel, A, Cardenas, A, Chiu, WA, Felsher, DW, Gibbons, CF, Goodson, WH, Houck, KA, Kane, A, La Merrill, MA, Lebrec, H, Lowe, L, McHale, CM, Minocherhomji, S, Rieswijk, L, Sandy, MS, Sone, H, Wang, A, Zhang, L, Zeise, L & Fielden, M 2020, 'The Key Characteristics of Carcinogens: Relationship to the Hallmarks of Cancer, Relevant Biomarkers, and Assays to Measure Them', Cancer Epidemiology Biomarkers & Prevention, vol. 29, no. 10, pp. 1887-1903. https://doi.org/10.1158/1055-9965.epi-19-1346

TY - JOUR

T1 - The Key Characteristics of Carcinogens

T2 - Relationship to the Hallmarks of Cancer, Relevant Biomarkers, and Assays to Measure Them

AU - Smith, Martyn T

AU - Guyton, Kathryn Z

AU - Kleinstreuer, Nicole

AU - Borrel, Alexandre

AU - Cardenas, Andres

AU - Chiu, Weihsueh A

AU - Felsher, Dean W

AU - Gibbons, Catherine F

AU - Goodson, William H

AU - Houck, Keith A

AU - Kane, Agnes

AU - La Merrill, Michele A

AU - Lebrec, Herve

AU - Lowe, Leroy

AU - McHale, Cliona M

AU - Minocherhomji, Sheroy

AU - Rieswijk, Linda

AU - Sandy, Martha S

AU - Sone, Hideko

AU - Wang, Amy

AU - Zhang, Luoping

AU - Zeise, Lauren

AU - Fielden, Mark

PY - 2020/10

Y1 - 2020/10

N2 - BACKGROUND: The key characteristics (KCs) of human carcinogens provide a uniform approach to evaluating mechanistic evidence in cancer hazard identification. Refinements to the approach were requested by organizations and individuals applying the KCs.METHODS: We assembled an expert committee with knowledge of carcinogenesis and experience in applying the KCs in cancer hazard identification. We leveraged this expertise and an examination of the literature to more clearly describe each KC; identify current and emerging assays and in vivo biomarkers that can be used to measure them; and, make recommendations for future assay development.RESULTS: We found that the KCs are clearly distinct from the Hallmarks of Cancer, that interrelationships among the KCs can be leveraged to strengthen the KC approach (and an understanding of environmental carcinogenesis), and that the KC approach is applicable to the systematic evaluation of a broad range of potential cancer hazards in vivo and in vitro. We identified gaps in coverage of the KCs by current assays.CONCLUSION: Future efforts should expand the breadth, specificity and sensitivity of validated assays and biomarkers that can measure the 10 KCs.IMPACT: Refinement of the KC approach will enhance and accelerate carcinogen identification, a first step in cancer prevention.

AB - BACKGROUND: The key characteristics (KCs) of human carcinogens provide a uniform approach to evaluating mechanistic evidence in cancer hazard identification. Refinements to the approach were requested by organizations and individuals applying the KCs.METHODS: We assembled an expert committee with knowledge of carcinogenesis and experience in applying the KCs in cancer hazard identification. We leveraged this expertise and an examination of the literature to more clearly describe each KC; identify current and emerging assays and in vivo biomarkers that can be used to measure them; and, make recommendations for future assay development.RESULTS: We found that the KCs are clearly distinct from the Hallmarks of Cancer, that interrelationships among the KCs can be leveraged to strengthen the KC approach (and an understanding of environmental carcinogenesis), and that the KC approach is applicable to the systematic evaluation of a broad range of potential cancer hazards in vivo and in vitro. We identified gaps in coverage of the KCs by current assays.CONCLUSION: Future efforts should expand the breadth, specificity and sensitivity of validated assays and biomarkers that can measure the 10 KCs.IMPACT: Refinement of the KC approach will enhance and accelerate carcinogen identification, a first step in cancer prevention.

KW - ARYL-HYDROCARBON RECEPTOR

KW - IN-SILICO PREDICTION

KW - GENOMIC INSTABILITY

KW - REPLICATION STRESS

KW - OXIDATIVE STRESS

KW - BREAST-CANCER

KW - DNA-DAMAGE

KW - INFLAMMATORY BIOMARKERS

KW - CHROMOSOMAL-ABERRATIONS

KW - REACTIVE METABOLITES

U2 - 10.1158/1055-9965.epi-19-1346

DO - 10.1158/1055-9965.epi-19-1346

M3 - Article

C2 - 32152214

VL - 29

SP - 1887

EP - 1903

JO - Cancer Epidemiology Biomarkers & Prevention

JF - Cancer Epidemiology Biomarkers & Prevention

SN - 1055-9965

IS - 10

ER -