Table 3.

A therapeutic target to decrease breast cancer metastasis

Treatment	Description	Mechanism
ADGRG1 inhibitors [150]	ADGRG1 is a protein that actively facilitates the process of tumorigenesis, invasion/migration, and cell–cell adhesion in cells associated with triple-negative breast cancer	Inhibitors of ADGRG1 could prevent CTC cluster formation by blocking its role in cell–cell adhesion
Estrogen receptor alpha (ER/ESR1) inhibitors [151]	Mutations in ER/ESR1 have been detected in 20–40% of metastatic breast cancers resistant to endocrine therapy. These mutations are linked to unfavorable outcomes	Inhibitors of ER/ESR1 could prevent CTC cluster formation by blocking its role in metastasis
Chemotherapy drugs [152]	Chemotherapy is the prevailing approach for managing systemic therapy in triple-negative breast cancer (TNBC) patients	It can still effectively prevent CTC cluster formation by killing cancer cells and preventing their spread
Customized drug screening [153]	A culture assay of CTC derived from patients can be a valuable tool for evaluating anticancer drugs to guide therapy for personalized treatment	This approach allows for evaluating drug response using patient-derived CTC cultures obtained from a liquid biopsy
VEGF inhibitors [55]	The protein VEGF serves to activate the genesis of novel blood vessels	The growth of new blood vessels that provide tumors with oxygen and nutrients exists through inhibitors that target VEGF
Pro-angiogenic treatment [55]	The pro-angiogenic treatment promotes the genesis of novel blood vessels	This treatment could improve blood flow to tumors, allowing for better chemotherapy drugs and oxygen delivery
Epigen [154]	Clusters promoted the expression of the low-affinity EGFR ligand epigen, which promotes effective metastatic outgrowth and is exhibited in the highest levels in metastatic tumors	The metastatic outgrowth was reduced by 94% upon Epigen knockdown. Additionally, there was a decrease in the size of lung metastases, although the total number was not affected
Plakoglobin [155]	Plakoglobin, a component of desmosomes and adherence junctions, was overexpressed 219-fold more in CTC clusters and was associated with lower distant metastasis-free survival (p = 0.008)	Eliminating intercellular contacts crucial for cluster formation was achieved through Plakoglobin knockdown, and the count of tumor-derived CTC clusters decreased in experimental mouse tumors
Keratin-14 [45]	Desmosome and hemidesmosome adhesion complex genes, which control cell–matrix adhesion, cell–cell adhesion, and immune evasion, were abundant in keratin 14 cells	The mean number of metastases was seven times lower in keratin 14 knockdown tumors than in control tumors
ICAM-1 [156]	ICAM-1 is a transmembrane glycoprotein crucial for melanoma cells' adhesion to the endothelial monolayer [124]	ICAM-1 expression is increased with an increase in tumor cell adhesion. Thus, treatment with specific anti-ICAM-1 antibodies decreases this effect
Hemophilic CD44 [157]	CD44, a multifaceted transmembrane glycoprotein, facilitates the epithelial-mesenchymal transition process [126]	CD44-positive cells exhibited a heightened propensity for tumor formation in immunodeficient mice relative to their CD44-negative counterparts
Na + /K + ATPase inhibitor [158, 159]	Na + /K + ATPase exists on the cell membrane; its expression is highly expressed in breast cancer cases	Ouabain treatment inhibits the expression of Na + /K + ATPase in mice, which inhibits distant tumor formation in multiple mouse metastasis models