The effect of the CDK7 inhibitor TGN-1062 on neuroblastoma cancer cells
Neuroblastoma is a rare pediatric cancer commonly affecting children under the age of five and causes 15% of all pediatric cancer deaths. Of those afflicted with neuroblastoma, 25% of cases include the amplification of an oncogene called N-myc and this amplification is correlated with poorer patient prognosis and less response to traditional treatment. Direct N-myc inhibition as treatment has been unsuccessful. However, N-mycexpression is controlled by CDK7, an important cell cycle and transcription regulator, and inhibition of CDK7 would inhibit N-myc and prevent tumor proliferation. A potent, reversible CDK7 inhibitor called “TGN-1062” has been developed by our laboratory and has been tested as an effective therapeutic in multiple cancer types, but has yet to be tested on neuroblastoma. To evaluate TGN-1062’s CDK7 inhibition in N-myc amplified neuroblastoma cells, viability assays and western blotting were performed. TGN-1062 inhibited growth of both N-myc amplified and non-amplified cell lines with varying potency. Western blotting showed a decrease in the expression of N-myc and its target MCL1 in response to treatment with TGN-1062. We also combined TGN-1062 with other approved cancer therapeutics (Ponatinib and Vorinostat) and determined that there is a potential for combination with these compounds. In conclusion, our results suggest that targeting CDK7 may provide a novel option for neuroblastoma cancer therapy.
