The present invention relates to methods and compositions designed for the treatment, management, or prevention of a hypoproliferative
cell disorder, especially those disorders relating to the destruction, shedding, or inadequate proliferation of epithelial and / or endothelial cells, particularly
interstitial cystitis (IC) and lesions associated with
inflammatory bowel disease (IBD). The methods of the invention comprise the administration of an effective amount of one or more agents that are antagonists of EphA2. In certain embodiments, the EphA2 antagonistic agent of the invention decreases EphA2-endogenous ligand binding, upregulates EphA2
gene expression and / or translation, increases EphA2
protein stability or
protein accumulation, decreases EphA2 cytoplasmic
tail phosphorylation, promotes EphA2
kinase activity (other than
autophosphorylation or ligand-mediated EphA2 signaling), increases proliferation of EphA2 expressing cells, increases survival of EphA2 expressing cells, and / or maintains / reconstitutes epithelial and / or endothelial
cell layer integrity. The invention also provides pharmaceutical compositions comprising one or more EphA2 antagonistic agents of the invention either alone or in combination with one or more other agents useful for therapy for a hypoproliferative
cell disorder.
Diagnostic methods and methods for screening for therapeutically useful agents are also provided.