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

Research output: Contribution to journalArticleAcademicpeer-review

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 languageEnglish
JournalCancer Epidemiology Biomarkers & Prevention
DOIs
Publication statusE-pub ahead of print - 9 Mar 2020

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. https://doi.org/10.1158/1055-9965.EPI-19-1346