Preclinical Evaluation of Combined Targeted Approaches in Malignant Rhabdoid Tumors.

BACKGROUND/AIM: Rhabdoid tumors (RT) are aggressive pediatric tumors, which show poor prognosis despite use of multimodal intensive therapy. In these tumors, several different oncogenic pathways and epigenetic regulators (like CDK4/6-cyclinD-Rb-signaling, EZH2, histone deacetylases) are contemporaneously deregulated as a consequence of biallelic SMARCB1/SNF5/INI1 alterations. Since these tumors are highly resistant to current therapies, alternative treatment strategies are urgently required.

MATERIALS AND METHODS: In this study, we evaluated cytotoxic effects (by MTT tests) of small molecular compounds, which specifically target these deregulated pathways, using either single-drug or combined approaches. Half-maximal inhibitory concentration (IC50) and combined index (CI) were calculated.

RESULTS: All target-directed inhibitors blocked cell growth of three different rhabdoid tumor cell lines in vitro. Several combinations of those target-specific drugs synergistically inhibited cell proliferation of rhabdoid tumors.

CONCLUSION: Supporting earlier reports, combined target-directed approaches are a promising tool for the therapy of malignant rhabdoid tumors.