[Federal Register Volume 84, Number 33 (Tuesday, February 19, 2019)]
[Pages 4831-4832]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-02683]



National Institutes of Health

Request for Information (RFI) on Assays and Approaches for 
Evaluating Chemical Effects on Cancer Pathways

AGENCY: National Institutes of Health, HHS.

ACTION: Request for information.


SUMMARY: The National Toxicology Program (NTP) at the National 
Institute of Environmental Health Sciences is seeking input on assays 
and approaches for evaluating chemical effects on cancer pathways, 
specifically, pathways that map to the hallmarks of cancer and key 
characteristics of carcinogens.

DATES: The National Toxicology Program's Request for Information is 
open for public comment for a period of 60 days. Comments must be 
received by April 22, 2019 to ensure consideration. After the public 
comment period has closed, the comments received by the NTP will be 
used to inform the April 29-30th Workshop Converging on Cancer (https://ntp.niehs.nih.gov/go/coc). All responses to information requested in 
this RFI are voluntary.

ADDRESSES: Submissions may be electronically to https://ntp.niehs.nih.gov/go/COC_RFI or by mail to Cynthia Rider, Ph.D., 
National Institute of Environmental Health Sciences, 111 TW Alexander 
Drive, PO Box 12233, MD:K2-12, Research Triangle Park, NC 27709.

FOR FURTHER INFORMATION CONTACT: Questions about this request for 
information should be directed to FOR FURTHER INFORMATION CONTACT: 
Questions about this request for information should be directed to 
Cynthia Rider, Ph.D., National Institute of Environmental Health 
Sciences, 111 TW Alexander Drive, PO Box 12233, MD:K2-12, Research 
Triangle Park, NC 27709, [email protected], 984-287-3175.

SUPPLEMENTARY INFORMATION: Cancer is a leading cause of mortality 
worldwide. While the defining feature of cancer is uncontrolled 
division of abnormal cells, it is a complex disease with varied 
presentations (i.e., different etiologies and target tissues) that 
involves dysregulation of multiple interconnected signaling pathways. 
Diverse environmental factors have been associated with the development 
and progression of various cancer types. A critical question in the 
field of environmental health is how to harness what is known about 
cancer biology and associated environmental exposures to improve public 
health outcomes. This Request for Information is in support of the 
Converging on Cancer Workshop, which is aimed at providing a clear path 
forward for evaluating the interactions between environmental exposures 
and cancer biology using the latest tools in toxicology and identifying 
knowledge gaps that require research attention. Potential applications 
of this understanding include building a framework for incorporating 
mechanistic data into cancer risk assessment, developing efficient and 
reliable screening tools to detect the carcinogenic potential of 
environmental chemicals (including mixtures), engineering safer 
products, and designing more effective multi-target therapeutics.
    The hallmarks of cancer (1) and key characteristics of carcinogens 
(2) offer two paradigms for organizing information to better understand 
the interactions between environmental exposures and biological systems 
that lead to cancer. The hallmarks of cancer represent the biological 
traits of tumors that allow for the unchecked growth of cancer, while 
the key characteristics framework begins with known human carcinogens 
and identifies their defining properties. It is clear from 
biomonitoring studies that we are constantly exposed to numerous 
structurally-diverse chemicals. A recent nomination to NTP was for 
development of a testing strategy to better understand how 
environmental chemicals might interact with multiple cancer-relevant 
biological pathways to elicit mixture effects that would not be 
expected based on single chemical considerations. This RFI is intended 
to generate input that will facilitate new testing approaches designed 
to evaluate these hypotheses in a cancer context. Responses to the RFI 
should provide information on technologies targeting cancer-specific 
pathways and mechanisms, including organotypic and/or mechanistically 
insightful tools, preferred animal models, and in silico/computational 
approaches to link relevant pathways, as well as cancer types for use 
in evaluating hypotheses regarding the joint action of chemicals that 
target cancer pathways.
    Information requested: The NTP requests information regarding 
assays and approaches to measure the key biological mechanisms/pathways 
associated with chemical carcinogenesis. Responses to any or all of the 
questions below are invited from interested individuals/groups, 
including, but not limited to, the environmental health research 
community, health professionals, educators, policy makers, industry, 
and the public.
     Systematic review approaches to transparently identify and 
evaluate mechanistic information on the carcinogenic properties of 
chemicals and chemical mixtures.
     Assays associated with the biological mechanisms/pathways 
described by the hallmarks of cancer and the key characteristics of 
     Assays that integrate across multiple cancer-related 
pathways (e.g., organotypic microphysiological systems, mechanistic 
animal models).
     Modeling approaches to assess the joint effects of 
multiple chemicals on carcinogenic potential.
     Feedback on critical pathways and mechanisms to target 
when developing novel carcinogenicity testing strategies.
     Feedback on cancer types conducive to exploring chemical 
interaction hypotheses.
     Environmental chemicals known to affect key biological 
mechanisms/pathways leading to cancer and which key biological 
mechanisms/pathways are affected by these chemicals.

[[Page 4832]]

     Types of scientific data (e.g., mechanistic, 
epidemiological) needed to address underlying knowledge gaps of 
chemical exposures leading to carcinogenesis.
     New technologies and innovative research approaches that 
could be leveraged to address these underlying knowledge gaps.


1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. 
Cell. 2011;144(5):646-74. doi: 10.1016/j.cell.2011.02.013. PubMed 
PMID: 21376230.
2. Smith MT, Guyton KZ, Gibbons CF, Fritz JM, Portier CJ, Rusyn I, 
et al. Key Characteristics of Carcinogens as a Basis for Organizing 
Data on Mechanisms of Carcinogenesis. Environmental health 
perspectives. 2016;124(6):713-21. doi: 10.1289/ehp.1509912. PubMed 
PMID: 26600562; PubMed Central PMCID: PMC4892922.

Brian R. Berridge,
Associate Director, National Toxicology Program, National Institute of 
Environmental Health Sciences.
[FR Doc. 2019-02683 Filed 2-15-19; 8:45 am]