TACSTD2

Official Full Name

tumor associated calcium signal transducer 2

Organism

Homo sapiens

GeneID

4070

Background

This intronless gene encodes a carcinoma-associated antigen. This antigen is a cell surface receptor that transduces calcium signals. Mutations of this gene have been associated with gelatinous drop-like corneal dystrophy.[provided by RefSeq, Dec 2009]

Synonyms

EGP1; GP50; M1S1; EGP-1; TROP2; GA7331; GA733-1;

Protein Sequence

MARGPGLAPPPLRLPLLLLVLAAVTGHTAAQDNCTCPTNKMTVCSPDGPGGRCQCRALGSGMAVDCSTLTSKCLLLKARMSAPKNARTLVRPSEHALVDNDGLYDPDCDPEGRFKARQCNQTSVCWCVNSVGVRRTDKGDLSLRCDELVRTHHILIDLRHRPTAGAFNHSDLDAELRRLFRERYRLHPKFVAAVHYEQPTIQIELRQNTSQKAAGDVDIGDAAYYFERDIKGESLFQGRGGLDLRVRGEPLQVERTLIYYLDEIPPKFSMKRLTAGLIAVIVVVVVALVAGMAVLVITNRRKSGKYKKVEIKELGELRKEPSL

Open

Disease

Breast cancer, Non-small-cell lung cancer, Solid tumour/cancer, Ureteral cancer

Approved Drug

1 +

Clinical Trial Drug

1 +

Discontinued Drug

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Tag	Price

Cat.No.	Product Name	Price

Detailed Information

TACSTD2 (Tumor-Associated Calcium Signal Transducer 2), also known as TROP2, is located on human chromosome 1p32.1 and encodes a single-pass transmembrane glycoprotein, which belongs to the epithelial cell adhesion molecule (EPCAM) family. The structure of TROP2 includes an extracellular domain (containing tyrosine phosphorylation sites), a transmembrane region, and a cytoplasmic tail (containing a PI3K/AKT binding motif). TROP2 regulates cell-matrix adhesion through calcium ion signaling, and its expression is positively regulated by the Wnt/β-catenin signaling pathway. During embryonic development, TROP2 is involved in tissue morphogenesis, and in adult tissues, it is primarily expressed in regenerative tissues such as the cornea and intestinal epithelium.

Biological Function and Pathological Mechanisms

The dysfunction of TACSTD2 is associated with two distinct types of diseases. First, mutations in TACSTD2 are linked to corneal dystrophy, where mutations lead to protein misfolding and amyloid deposition beneath the corneal epithelium. Clinically, this results in the formation of grayish-white gelatinous nodules on the corneal surface and progressive vision loss, which is particularly prevalent in Asian populations. Secondly, TROP2 is overexpressed in various malignancies, especially in bladder cancer, where its expression level exceeds 90%. The oncogenic mechanism of TROP2 includes activating the PI3K/AKT/mTOR pathway to inhibit apoptosis, promoting the transcription of cell cycle protein Cyclin D1, and forming complexes with integrin β1–Claudin-7, which aids in tumor invasion and metastasis.

TROP2 expression is closely associated with tumor molecular subtypes. For instance, in bladder cancer, TROP2 levels are significantly higher in the urothelial carcinoma subtype compared to the squamous differentiation subtype, while neuroendocrine-like tumors exhibit a loss of expression.

Figure 1. Trop2-mediated intracellular and extracellular signaling pathways. (Liu X, et al., 2022)

Clinical Translation and Therapeutic Advancements

Due to the high expression of TROP2 in various cancers, it has become a prominent target for antibody-drug conjugates (ADC). Sacituzumab Govitecan (SG), an ADC consisting of an anti-TROP2 monoclonal antibody conjugated to the topoisomerase inhibitor SN-38, has shown significant therapeutic efficacy in metastatic triple-negative breast cancer (mTNBC). The objective response rate (ORR) was 35%, and the median overall survival (OS) was extended to 14.4 months, compared to 11.2 months in the chemotherapy group. In non-small cell lung cancer (NSCLC), another TROP2-targeting ADC, Datopotamab Deruxtecan (Dato-DXd), showed a significant improvement in progression-free survival (PFS) with a lower incidence of interstitial lung disease compared to similar drugs.

In addition to cancer treatment, gene therapy strategies are exploring how to correct TACSTD2 mutations. Using adeno-associated virus (AAV) vectors to deliver the wild-type TACSTD2 gene into the cornea in a GDLD mouse model successfully reduced amyloid deposits by 50%, providing a potential approach for treating genetic corneal diseases.

Challenges and Future Directions

Despite the promising potential of TROP2-targeted therapies, there are several challenges to address. First, the physiological expression of TROP2 in normal tissues, particularly in the intestinal epithelium, may lead to tissue toxicity, as seen with SG, where 11% of patients experienced severe diarrhea. Additionally, the internalization efficiency of ADCs may be compromised by the glycosylation modifications of TROP2. In bladder cancer, about 18.4% of tumors exhibit low TROP2 expression, which results in reduced internalization and decreased therapeutic response. Therefore, developing conditional activation antibodies or optimizing drug delivery systems could help improve therapeutic specificity and reduce side effects.

Future research should focus on the interaction between TROP2 and the immune microenvironment, exploring the co-expression of TROP2 and immune checkpoint molecules (e.g., PD-L1) to support the development of ADC-immunotherapy combination strategies. Additionally, integrating genomic and transcriptomic data to predict ADC responsiveness based on tumor subtypes (e.g., basal-like vs. luminal) and utilizing artificial intelligence to design more selective treatments could become key strategies for advancing TROP2-targeted therapies.

In conclusion, TROP2 plays a critical role in cancer cell proliferation, invasion, and metastasis and holds potential as a therapeutic target not only in cancer but also in genetic corneal diseases. As research advances in understanding its biological functions and developing more precise treatment strategies, TROP2 could become a pivotal target in both oncology and gene therapy, improving the treatment outcomes of various diseases.

Reference

Liu X, Deng J, Yuan Y, et al. Advances in Trop2-targeted therapy: Novel agents and opportunities beyond breast cancer. Pharmacol Ther. 2022 Nov;239:108296.
Liu X, Ma L, Li J, et al. Trop2-targeted therapies in solid tumors: advances and future directions. Theranostics. 2024 Jun 11;14(9):3674-3692.

Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry