Homotypic vs. Heterotypic Clustering

CTC clusters are groups of circulating tumor cells that travel together in the bloodstream and are markedly more metastatic than single CTCs. Homotypic clusters are formed of CTCs alone, stabilized by plakoglobin-dependent desmosomes and CD44 homophilic adhesion, while heterotypic clusters also include host cells such as platelets (via P-selectin/PSGL-1), neutrophils (via IL-6/IL-1β and ICAM-1), or cancer-associated fibroblasts (CAFs).

The Na⁺/K⁺-ATPase inhibitor digoxin can dissociate these clusters — in a Phase I trial (DICCT, NCT03928210), it reduced mean cluster size by 2.2 cells, though cardiotoxicity limits its clinical use.