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Cancer Therapeutic Targets

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Abstract

The APC gene is located at chr5q21 and is expressed in many tissues throughout the human body. In the colorectal epithelium in particular, APC functions as a critical suppressor of cancer initiation. Individuals who inherit inactivating mutations in one allele of the APC gene exhibit familial adenomatous polyposis (FAP) coli, an autosomal dominant syndrome characterized by the formation of a variety of benign lesions, particularly numerous adenomatous polyps of the colorectal epithelium. In the absence of preventative surgery to remove the source of these precancerous adenomas, FAP patients are highly susceptible to the development of colorectal cancer at an early age. Adenomas from FAP patients exhibit somatic mutations in the second allele of APC. Sporadically occurring colorectal adenomas in the general population frequently harbor biallelic APC mutations as well. The APC protein protects against adenoma formation in the colorectal epithelium at least in part by negatively regulating the canonical WNT signaling pathway. APC loss activates canonical WNT signaling, which coordinates changes in gene expression that promote proliferation over differentiation and cell survival over apoptosis. Ongoing research is focused on improving the accuracy of genetic screens for APC mutations, determining the extent to which colorectal cancers with APC mutations can be effectively treated with agents that downregulate canonical WNT signaling and testing the value of APC promoter hypermethylation as a diagnostic, prognostic, or predictive marker for other forms of cancer.

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Author information

Authors and Affiliations

  1. Molecular Virology, Immunology and Medical Genetics, The Ohio State University, 986 Biomedical Research Tower, 460 W. 12th Ave, Columbus, OH, 43210, USA

    Joanna Louise Groden

  2. College of Medicine, The Ohio State University, Columbus, Ohio, 43210, USA

    William Hankey

  3. The Ohio State University, Wexner Medical Center, 410 W. 10th Ave, Columbus, OH, 43210, USA

    Kenechi Ebede

Authors
  1. Joanna Louise Groden
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  2. William Hankey
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  3. Kenechi Ebede
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Corresponding author

Correspondence to Joanna Louise Groden .

Editor information

Editors and Affiliations

  1. Georgetown University Div. Hematology & Oncology, Washington, District of Columbia, USA

    John L. Marshall

Section Editor information

  1. Division of Hematology/Oncology, Herbert Irving Comprehensive Cancer Center, Columbia University, 1130 Saint Nicholas Avenue, ICRC 321A, 10032, New York, NY, USA

    Edward P. Gelmann

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Groden, J.L., Hankey, W., Ebede, K. (2016). APC. In: Marshall, J. (eds) Cancer Therapeutic Targets. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6613-0_58-4

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  • DOI: https://doi.org/10.1007/978-1-4614-6613-0_58-4

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  • Publisher Name: Springer, New York, NY

  • Online ISBN: 978-1-4614-6613-0

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

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Chapter history

  1. Latest

    APC
    Published:
    23 June 2016

    DOI: https://doi.org/10.1007/978-1-4614-6613-0_58-4

  2. Original

    APC
    Published:
    29 January 2016

    DOI: https://doi.org/10.1007/978-1-4614-6613-0_58-3

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