V-ATPase Inhibitors

V-ATPase inhibitors are a drug class explored for reversing anoikis resistance, including archazolid and digoxin (which acts via the related Na⁺/K⁺-ATPase).

Digoxin reduces anoikis resistance in both circulating and non-circulating cancer cells by promoting proteasomal degradation of the anti-apoptotic protein Mcl-1, and — in a separate context — dissociates circulating-tumor-cell clusters (DICCT trial, NCT03928210).