Collectively, based on our study, VERU-111 overcome Vem-resistance through the following mechanisms: 1) As a tubulin destabilizing agent, disrupt tubulin polymerization, promote microtubule fragmentation, inhibit cancer cell migration; 2) Combined with Vem, arresting cell both in G0-G1 and G2-M phase; 3) Compromised Skp2-AKT signaling pathway. Here, AKT1 is linked to cancer.