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Event: 885

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Increase, Cancer

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Increase, Cancer
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Tissue

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Process Object Action
Neoplasms increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
DNA alkylation -> cancer 2 AdverseOutcome Carole Yauk (send email) Not under active development
DNA alkylation -> cancer 1 AdverseOutcome Carole Yauk (send email) Open for adoption
ROS formation leads to cancer via inflammation pathway AdverseOutcome John Frisch (send email) Under development: Not open for comment. Do not cite
ROS formation leads to cancer via PPAR pathway AdverseOutcome John Frisch (send email) Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
Homo sapiens Homo sapiens High NCBI
Mus musculus Mus musculus High NCBI
Rattus norvegicus Rattus norvegicus High NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
All life stages High

Sex Applicability

An indication of the the relevant sex for this KE. More help
Term Evidence
Unspecific High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Cancer is a general key event for related diseases each exhibiting uncontrolled proliferation of abnormal cells (for review see Hanahan and Weinberg 2011).  A cancer often is initially associated with a specific organ, with malignant tumors developing ability to metastasize, or travel to other areas of the body.  Most cancers develop from genetic mutations in normal cells, although a minority of cancers are hereditary.   Exposure to chemical stressors, radiation, tobacco smoke, or viruses can increase the likelihood that cancer will develop.

Cancer cells proliferate due to capabilities summarized by Hanahan and Weinberg (2011):

  1. Sustained proliferation signaling – by deregulating normal cell signals, cancer cells can sustain chronic proliferation.
  2. Evading growth suppressors – by evading activities of tumor suppressor genes, cancer cells continue to proliferate.
  3. Activating invasion and metastasis – by altering shape and attachment to cells in the extracellular matrix, cancer cells gain ability to move to other locations.
  4. Enabling replicative immortality – by disabling senescence pathways, cancer cells have extended lifespans.
  5. Inducing angiogenesis – by enabling neovasculature, cancer cells receive nutrients and oxygen and get rid of waste products.
  6. Resisting cell death – by evading apotosis and necrosis defense pathways, cancer cells avoid elimination.

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Most carcinogenicity studies are conducted with rodents (see OECD 2018; Zhou et al. 2023 for methods) or in-vitro with mammalian cell lines (see OECD 2023 for methods).  Cancer is usually detected by biopsy or histopathological examination of tissue.  Gene expression levels can also be assessed, as increased transcription of known genes have been associated with specific cancers (ex. Tumor Necrosis Factor (Pavet et al. 2014); Heat Shock Factors (Vihervaara and Sistonen 2014; Androgen Receptor (Heinlein and Chang 2004)).

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

Life Stage: All life stages.  Older individuals are more likely to manifest this key event (adults > juveniles > embryos).

Sex: Applies to both males and females.

Taxonomic: Appears to be present broadly, with representative studies including mammals (humans, lab mice, lab rats), teleost fish, and invertebrates (cladocerans, mussels).

Regulatory Significance of the Adverse Outcome

An AO is a specialised KE that represents the end (an adverse outcome of regulatory significance) of an AOP. More help

Cancer is a critical endpoint in human health risk assessment.   It is embedded in regulatory frameworks for human health protection in many countries (see OSHA 2023 for examples of US regulations and European Parliament 2022 for examples of regulations in Europe).

References

List of the literature that was cited for this KE description. More help

Abraha, A.M. and Ketema, E.B.  2016.  Apoptotic pathways as a therapeutic target for colorectal cancer treatment.  World Journal of Gastrointestinal Oncology 8 (8): 583-491

European Parliament.  2022.  Directive 2004/37/EC of the European Parliament on the protection of workers from the risks related to exposure to carcinogens, mutagens or reprotoxic substances at work.  Retrieved 3 August 2023 from http://data.europa.eu/eli/dir/2004/37/2022-04-05

Hanahan, D. and Weinberg, R.A.  2011.  Hallmarks of cancer: the next generation.  Cell 144(5): 646-674.

Heinlein, C.A. and Chang, C.  2004.  Androgen receptor in prostate cancer.  Endocrine Reviews 25: 276-308.

OECD.  2018.  Test no. 451: OECD Guideline for the Testing of Chemicals: Carcinogenicity Studies.  OECD Publishing, Paris.  Retrieved 3 August 2023 from https://www.oecd.org/env/test-no-451-carcinogenicity-studies-9789264071186-en.htm

OECD.  2023. Test No. 487: In Vitro Mammalian Cell Micronucleus Test, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris.  Retrieved 3 August 2023 from  https://doi.org/10.1787/9789264264861-en.htm

OSHA. 2023.  Carcinogens.  Retrieved 3 August 2023 from https://www.osha.gov/carcinogens/standards

Pavet, V., Shlyakhtina, Y., He, T., Ceschin, D.G., Kohonen, P., Perala, M., Kallioniemi, O., and Gronemeyer, H.  2014.  Plasminogen activator urokinase expression reveals TRAIL responsiveness and support fractional survival of cancer cells.  Cell Death and Disease 5: e1043.

Vihervaara, A. and Sistonen, L.  2014.  HSF1 at a glance.  Journal of Cell Scientce 127: 261-266.

Zhou, Y., Xia, J., Xu, S., She, T., Zhang, Y., Sun, Y., Wen, M., Jiang, T., Xiong, Y., and Lei, J.  2023.  Experimental mouse models for translational human cancer research.  Frontiers in Immunology 14: 1095388.