Tumor-associated calcium signal transducer 2, also known as Trop-2 and as epithelial glycoprotein-1 antigen (EGP-1) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''TACSTD2''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. This

intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e., a region inside a gene."The notion of the cistron .e., gen ...

less gene is located at the short arm of chromosome 1 (1p32.1). It encodes a carcinoma-associated

antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

defined by the monoclonal antibody GA733. This antigen is a member of a family including at least two type I

membrane protein Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a cell membrane ...

s. It transduces an intracellular

calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...

signal and acts as a

cell surface receptor Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving (binding to) extracellular molecules. They are specialized integra ...

. Mutations of this gene result in gelatinous drop-like corneal dystrophy, an

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

disorder characterized by severe corneal

amyloidosis Amyloidosis is a group of diseases in which abnormal proteins, known as amyloid fibrils, build up in tissue. There are several non-specific and vague signs and symptoms associated with amyloidosis. These include fatigue, peripheral edema, weigh ...

leading to

blindness Visual or vision impairment (VI or VIP) is the partial or total inability of visual perception. In the absence of treatment such as corrective eyewear, assistive devices, and medical treatment, visual impairment may cause the individual difficul ...

. Trop-2 expression was originally described in trophoblasts (placenta) and fetal tissues (e.g., lung). Later, its expression was also described in the normal stratified squamous epithelium of the skin, uterine cervix, esophagus, and tonsillar crypts. Trop-2 plays a role in tumor progression by actively interacting with several key molecular signaling pathways traditionally associated with cancer development and progression. Aberrant overexpression of Trop-2 has been described in several solid cancers, such as colorectal, renal, lung, and breast cancers. Trop-2 expression has also been described in some rare and aggressive malignancies, e.g., salivary duct, anaplastic thyroid, uterine/ovarian, and neuroendocrine prostate cancers. This overexpression is caused by deregulations at a transcriptional and posttranscriptional level. Trop-2 causes cancer cell growth, proliferation, invasion, migration, and survival of cancer cells, which leads to Trop-2 being associated with tumor aggressiveness and poor prognosis. This is also confirmed by the fact, that the proliferation of tumor cells is disturbed when Trop-2 is knocked down. These facts make Trop-2 a possible prognostic biomarker to identify high-risk patients, as well as an attractive therapeutic target for late-stage diseases This antigen is the target of

sacituzumab govitecan Sacituzumab govitecan, sold under the brand name Trodelvy by Gilead Sciences, is a Trop-2-directed antibody and topoisomerase inhibitor drug conjugate used for the treatment of metastatic triple-negative breast cancer and metastatic urothelial ...

and datopotamab deruxtecan (Dato-DXd),Datopotamab deruxtecan showed clinically meaningful overall survival improvement vs. chemotherapy in patients with advanced nonsquamous non-small cell lung cancer in TROPION-Lung01 Phase III tri

/ref> both antibody-drug conjugates.

References

Further reading