Efficacy of novel anti-CDK compounds to combat the invasion of HCC cells

The chemotherapeutic treatment of HCC is still very ineffective since most HCC patients escape from treatment with chemotherapeutics by resistance against anti-cancer drugs. We evaluated the therapeutic potential of novel cyclin-dependent kinase (CDK) inhibitors for treatment of HCC and found strong cytostatic and cytotoxic effects on HCC cell lines in vitro and in hepatoma xenograft models in vivo. These anti-proliferative effects were maintained after long-term exposure of HCC cells to CDK inhibitors, suggesting a high drug efficacy in the absence of chemoresistance. Most notably, these data suggest a superior efficacy compared to available chemotherapeutics in HCC. Current studies focus on the ability of anti-CDK compounds to diminish cell invasion of malignant hepatocytes in homotypic 3D hepatospheres. We particularly concentrate on antagonizing CDK8 and CDK9 and on analyzing its impact on the reversion of EMT and metastatic abilities. The putative multiple inhibitory roles of novel anti-CDK compounds in proliferation and invasion of HCC make them promising new drugs that must be considered for clinical investigation.