国际癌症研究机构致癌物关键特性研讨会：评估用于评价致癌危害机制证据的终点指标
IARC Workshop on the Key Characteristics of Carcinogens: Assessment of End Points for Evaluating Mechanistic Evidence of Carcinogenic Hazards.
作者信息
DeMarini David M, Gwinn William, Watkins Emily, Reisfeld Brad, Chiu Weihsueh A, Zeise Lauren, Barupal Dinesh, Bhatti Parveen, Cross Kevin, Dogliotti Eugenia, Fritz Jason M, Germolec Dori, Andersen Maria Helena Guerra, Guyton Kathryn Z, Jinot Jennifer, Phillips David H, Reddel Roger R, Rothman Nathaniel, van den Berg Martin, Vermeulen Roel C H, Vineis Paolo, Wang Amy, Whelan Maurice, Ghantous Akram, Korenjak Michael, Zavadil Jiri, Herceg Zdenko, Perdomo Sandra, Dossus Laure, Chittiboyina Shirisha, Cuomo Danila, Kaldor John, Pasqual Elisa, Rigutto Gabrielle, Wedekind Roland, Facchin Caterina, El Ghissassi Fatiha, de Conti Aline, Schubauer-Berigan Mary K, Madia Federica
机构信息
US Environmental Protection Agency (EPA; Retired), Research Triangle Park, North Carolina, USA.
Division of Translational Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park, North Carolina, USA.
出版信息
Environ Health Perspect. 2025 Feb;133(2):25001. doi: 10.1289/EHP15389. Epub 2025 Feb 3.
BACKGROUND
The 10 key characteristics (KCs) of carcinogens form the basis of a framework to identify, organize, and evaluate mechanistic evidence relevant to carcinogenic hazard identification. The 10 KCs are related to mechanisms by which carcinogens cause cancer. The () programme has successfully applied the KCs framework for the mechanistic evaluation of different types of exposures, including chemicals, metals, and complex exposures, such as environmental, occupational, or dietary exposures. The use of this framework has significantly enhanced the identification and organization of relevant mechanistic data, minimized bias in evaluations, and enriched the knowledge base regarding the mechanisms of known and suspected carcinogens.
OBJECTIVES
We sought to report the main outcomes of an IARC Scientific Workshop convened by the IARC to establish appropriate, transparent, and uniform application of the KCs in future evaluations.
METHODS
A group of experts from different disciplines reviewed the experience with the KCs of carcinogens, discussing three main themes: ) the interpretation of end points forming the evidence base for the KCs, ) the incorporation of data from novel assays on the KCs, and ) the integration of the mechanistic evidence as part of cancer hazard identification. The workshop participants assessed the relevance and the informativeness of multiple KCs-associated end points for the evaluation of mechanistic evidence in studies of exposed humans and experimental systems.
DISCUSSION
Consensus was reached on how to enhance the use of , molecular, and cellular high-output and high-throughput data. In addition, approaches to integrate evidence across the KCs and opportunities to improve methodologies of mechanistic evaluation of cancer hazards were explored. The findings described herein and in a forthcoming IARC technical report will support future working groups of experts in reporting and interpreting results under the KCs framework within the or in other contexts. https://doi.org/10.1289/EHP15389.
背景
致癌物的10个关键特征（KC）构成了一个框架的基础，该框架用于识别、组织和评估与致癌危害识别相关的机制证据。这10个关键特征与致癌物导致癌症的机制有关。（）项目已成功将关键特征框架应用于不同类型暴露的机制评估，包括化学物质、金属以及环境、职业或饮食暴露等复杂暴露。该框架的使用显著增强了相关机制数据的识别和组织，最大限度地减少了评估中的偏差，并丰富了关于已知和疑似致癌物机制的知识库。
目的
我们试图报告国际癌症研究机构（IARC）召开的一次科学研讨会的主要成果，该研讨会旨在确定在未来评估中对关键特征进行适当、透明和统一的应用。
方法
一组来自不同学科的专家回顾了致癌物关键特征的经验，讨论了三个主要主题：）构成关键特征证据基础的终点的解释，）将来自关键特征新检测方法的数据纳入，以及）将机制证据整合为癌症危害识别的一部分。研讨会参与者评估了多个与关键特征相关的终点对于评估暴露人群和实验系统研究中机制证据的相关性和信息量。
讨论
就如何加强对分子、细胞高产出和高通量数据的使用达成了共识。此外，还探讨了整合关键特征证据的方法以及改进癌症危害机制评估方法的机会。本文以及即将发表的IARC技术报告中描述的研究结果将支持未来的专家工作组在国际癌症研究机构或其他背景下的关键特征框架内报告和解释结果。https://doi.org/10.1289/EHP15389 。
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