EphA2 gene targeting using neutral liposomal small interfering RNA (EPHARNA) delivery: A phase I clinical trial.

TPS2604Background: EphA2 is a member of the largest subfamily of receptor tyrosine kinases, with over 14 receptors and 8 ligands. EphA2 overexpression is common in many human cancers, including lung, breast, prostate, colorectal, pancreatic, melanoma, esophageal and endometrial cancers. EphA2 can function as an oncoprotein when introduced into cells with low expression. In addition, downregulation of constitutive expression reduces tumorigenicity in breast, endometrial, ovarian and pancreatic cancers in vitro and in vivo models. EphA2 is a desirable target because of its selective expression in cancer (vs. adult normal tissue), and its important role in promoting tumor growth and metastasis. It has kinase-dependent and independent functions, making it an ideal target for RNAi-based targeting. We have previously reported that EphA2 siRNA incorporated in DOPC nanoliposomes (EPHARNA) was highly effective in reducing EphA2 protein levels after a single dose. In addition, three weeks of treatment with EPHARNA ...