UC San Diego

Prostate cancer remains the second leading cause of cancer death among men over 50 years old in the United States. Docetaxel is a taxane drug currently being used as a chemotherapy for advanced prostate cancer. However, prostate cancer patients often develop resistance to chemotherapy drugs. Therefore, we are interested in investigating new pathways that have the potential to overcome this resistance. From preliminary, independent analyses of ours and others, two new pathways have been shown to be important in advanced, therapy-resistant prostate cancer: ROR1 and CLIC1. ROR1 is the Receptor tyrosine kinase-like orphan receptor 1, an onco-embryonic antigen, which binds the WNT5A ligand and mediates non-canonical WNT signaling. The Chloride intracellular channel protein 1 (CLIC1) is known to be an important biomarker in several cancer types including prostate cancer. We sought to investigate the potential synergy of inhibitory therapies targeting ROR1 and CLIC1 with docetaxel. We hypothesized ROR1 and CLIC1 pathways as potential targets for therapies that can work either alone or in synergy with Docetaxel to inhibit prostate cancer progression. In this study, we sought to investigate the effect on cell proliferation and cell cycle of Docetaxel treatment and the inhibition of ROR1 and CLIC1 pathways. Through the optimization of cell-based assays using the Incucyte live cell microscope imaging technology, Docetaxel’s inhibitory effects on cell proliferation via G2 arrest was confirmed. Strikingly, our results revealed that without ROR1 expression, Docetaxel treatment leads to increased inhibition of cell proliferation, which we predict could lead to better outcomes in the clinic.