IDENTIFICATION OF NEW MOLECULAR TARGETS FOR TREATMENT OF ENDOMETRIAL CANCER

Abstract

The current treatment strategies for endometrial cancer include chemotherapy, surgery, and radiotherapy. However, the treatment results in huge variation in response rates and adverse effects. Although the new molecularly targeted drugs have been understood, the results from clinical trials remain unsatisfactory. Hence, there is a need to identify new molecular targets for the treatment of endometrial cancer. In this project, high-throughput screening was performed using a shRNA kinome library in endometrial cancer cell lines. It was found that the depletion of endogenous cyclin-dependent kinases regulatory subunit 1B (CKS1B) induces significant cell death in a panel of endometrial cancer cell lines. In contrast, no significant toxicity was observed in the non-transformed endometrial epithelial cells, suggesting that CKS1B mediates a tumour-specific survival pathway. In addition, immunoblotting assay showed that p27 protein expression was increased following the depletion of endogenous CKS1B in the type II endometrial cancer cells, while no changes was observed in the type I endometrial cancer cells. These results demonstrated that CKS1B regulates the survival of type I and type II endometrial cancer cells through distinct mechanisms. This suggests that the CKS1B could be a potential target for therapeutic intervention and warrants further investigation.