60 mg (∼35 mg/m2) given twice weekly in a 4-week cycle based on the totality of safety and efficacy data.

To determine whether inhibition of cell growth was due to an alteration in the cell cycle, we analyzed cell cycle distribution of Anaplastic thyroid carcinoma (ATC) cells either exposed to various concentrations (0–1000 nM, 48 h) of selinexor or XPO1 was silenced by transfection with XPO1 shRNA. XPO1 inhibition significantly increased G1 phase and decreased the S and G2/M phases in ATC cells. Of note, selinexor treatment resulted in cell cycle arrest in a dose-dependent manner. Further, was observed that selinexor altered the expression of its known cargo proteins (e.g., p53, p27 and p21), as well as indirect targets including cyclin B1, cyclin D1 in the ATC cell lines. Selinexor treatment (1000 nM, 24 h) also increased cleaved PARP, cleaved caspase-9 and cleaved caspase-3 in ATC cells. Cleavage of PARP [poly (ADP-ribose) polymerase is one of the hallmarks of apoptosis and caspase activation. This was associated with a decrease in the protein levels of anti-apoptotic proteins such as MCL1 and C-Myc. Moreover, was evaluated the dose-dependent effect of selinexor on the protein expression of a few important genes in CAL62 cells