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. 2020 Oct;29(10):1887-1903.
doi: 10.1158/1055-9965.EPI-19-1346. Epub 2020 Mar 9.

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

Martyn T Smith  1 , Kathryn Z Guyton  2 , Nicole Kleinstreuer  3   4 , Alexandre Borrel  3 , Andres Cardenas  5 , Weihsueh A Chiu  6 , Dean W Felsher  7 , Catherine F Gibbons  8 , William H Goodson 3rd  9 , Keith A Houck  10 , Agnes B Kane  11 , Michele A La Merrill  12 , Herve Lebrec  13 , Leroy Lowe  14 , Cliona M McHale  5 , Sheroy Minocherhomji  13 , Linda Rieswijk  5   15 , Martha S Sandy  16 , Hideko Sone  17 , Amy Wang  18 , Luoping Zhang  5 , Lauren Zeise  16 , Mark Fielden  19
Affiliations

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

Martyn T Smith et al. Cancer Epidemiol Biomarkers Prev. 2020 Oct.

Abstract

The key characteristics (KC) 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. We assembled an expert committee with knowledge of carcinogenesis and experience in applying the KCs in cancer hazard identification. We leveraged this expertise and examined 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. 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. Future efforts should expand the breadth, specificity, and sensitivity of validated assays and biomarkers that can measure the 10 KCs. Refinement of the KC approach will enhance and accelerate carcinogen identification, a first step in cancer prevention.See all articles in this CEBP Focus section, "Environmental Carcinogenesis: Pathways to Prevention."

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Conflict of interest statement

Conflict of Interest Statement: MTS has received consulting fees from attorneys representing plaintiffs in cases involving exposure to benzene, glyphosate and other chemical agents. DWF has received consulting fees from attorneys in cases involving exposure to asbestos, PCBs, TCE and other chemical agents. SM and HL are employees of Amgen. MF was an employee of Amgen during the initial meetings and is currently an employee of Expansion Therapeutics. The other authors declare no competing interests. The views expressed in this publication are those of the authors and do not necessarily represent the decisions, policy or views of their respective institutions. Reference to commercial products or services does not constitute endorsement.

Figures

Figure 1
Figure 1. The Hallmarks of Cancer and the Key Characteristics of Carcinogens
A. List of the Hallmarks of cancer. The Hallmarks of cancer, acquired properties of cancer cells that distinguish them from normal cells, have been described by Hanahan and Weinberg (1,2). Six Hallmarks were described in 2000 (1) and two emerging hallmarks (deregulated metabolism and immune system evasion) and two enabling characteristics (genome instability and inflammation) were added in 2011 (2). B. Symbolic illustration of the Hallmarks of cancer. C. List of the key characteristics of human carcinogens. The 10 key characteristics of human carcinogens describe the properties of human carcinogens that induce cancer (5). Expert participants at two IARC-led workshops initiated the development of the key characteristics based on empirical observations of the chemical and biological properties associated with the human carcinogens identified by the IARC Monographs program up to and including Volume 100. D. Symbolic illustration of the key characteristics of human carcinogens. Reprinted with permission from (203) Guyton KZ, Rieswijk L, Wang A, Chiu W, Smith MT (2018). Key characteristics approach to carcinogenic hazard identification. Chemical Research in Toxicology. 31(12):1290–1292. Copyright (2018) American Chemical Society
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References

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