Clinical Rationale for Targeting CEACAM5

CEACAM5 is a member of the CEACAM family of glycoproteins. It is a cell adhesion molecule that¹:

in normal and tumor tissues, connects adjacent cell membranes¹
when overexpressed, inhibits differentiation and apoptosis^2-4
when overexpressed, disrupts cell polarization and tissue architecture³

inhibits natural killer cytotoxicity by interacting with natural killer inhibitory receptor CEACAM1¹
as a soluble form, CEACAM5 induces pro-inflammatory cytokines that increase binding of circulating tumor cells to the endothelium¹

When levels are elevated, CEACAM5 may contribute to tumor development and metastasis through several mechanisms.¹

The discovery of CEA and the CEACAM family¹

CEACAM5, formerly known as CEA (carcinoembryonic antigen), was first discovered as a tumor-associated antigen for colorectal carcinoma.

This discovery led to the further identification of other CEA-related proteins, later unified under the name CEACAM family.

12 glycoproteins of the human CEACAM family^1,5

12 glycoproteins of the human CEACAM family.

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IgV-like domains
IgC2-like domains stabilized by disulfide bonds

transmembrane helices
ending in the lipid bilayer (GPI anchors)

Adapted from Beauchemin et al. Cancer Metastasis Rev. 2013;32(3-4):643-671¹; Hammarström. Semin Cancer Biol. 1999;9(2):67-81.⁵

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Beauchemin N, Arabzadeh A. Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) in cancer progression and metastasis. Cancer Metastasis Rev. 2013;32(3-4):643-671.
Eidelman FJ, Fuks A, DeMarte L, Taheri M, Stanners CP. Human carcinoembryonic antigen, an intercellular adhesion molecule, blocks fusion and differentiation in rat myoblasts. J Cell Biol. 1993;123(2):467-475.
Ordoñez C, Screaton RA, Ilantzis C, Stanners CP. Human carcinoembryonic antigen functions as a general inhibitor of anoikis. Cancer Res. 2000;60(13):3419-3424.
Ilantzis C, DeMarte L, Screaton RA, Stanners CP. Deregulated expression of the human tumor marker CEA and CEA family member CEACAM6 disrupts tissue architecture and blocks colonocyte differentiation. Neoplasia. 2002;4(2):151-163.
Hammarström S. The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. Semin Cancer Biol. 1999;9(2):67-81.