Novel treatment options are needed for
testicular germ cell tumor (TGCT) patients, particularly important for those showing or developing
cisplatin resistance, the major cause of
cancer-related deaths. As TGCTs pathobiology is highly related to epigenetic (de)regulation, epidrugs are potentially effective
therapies. Hence, we sought to explore, for the first time, the effect of the two most recently FDA-approved
HDAC inhibitors (HDACis),
belinostat and
panobinostat, in (T)GCT cell lines including those resistant to
cisplatin. In silico results were validated in 261 patient samples and differential expression of HDACs was also observed across cell lines.
Belinostat and
panobinostat reduced cell viability in both
cisplatin-sensitive cells (NCCIT-P, 2102Ep-P, and NT2-P) and, importantly, also in matched
cisplatin-resistant subclones (NCCIT-R, 2102Ep-R, and NT2-R), with IC50s in the low nanomolar range for all cell lines. Treatment of NCCIT-R with both drugs increased acetylation, induced cell cycle arrest, reduced proliferation, decreased Ki67 index, and increased p21, while increasing cell death by apoptosis, with upregulation of cleaved
caspase 3. These findings support the effectiveness of HDACis for treating TGCT patients in general, including those developing
cisplatin resistance. Future studies should explore them as single or combination agents.