Treatment of disease states which result from neoplastic cell proliferation using PPAR-γ activators and compositions useful therefor

Abstract

In accordance with the present invention, it has been discovered that PPARγ is expressed consistently in tissues associated with each of a variety of disease states which result from neoplastic cell proliferation. It has further been discovered that maximal activation of PPARγ with exogenous ligand promotes terminal differentiation of primary cells which are otherwise subject to neoplastic cell proliferation. In accordance with another aspect of the invention, it has been discovered that RXR-specific ligands are also potent agents for induction of differentiation of cells expressing the PPARγ/RXRα heterodimer, and that simultaneous treatment of cells subject to neoplastic cell proliferation with a PPARγ-selective ligand, in combination with an RXR-specific ligand, results in an additive stimulation of differentiation. Thus, the effect of neoplastic cell proliferation can be ameliorated by treatment of cells undergoing neoplastic cell proliferation with PPARγ agonists, optionally in the further presence of RXR agonists, thereby blocking further proliferation thereof. Accordingly, compounds and compositions which are useful for the treatment of a variety of disease states which result from neoplastic cell proliferation have been identified and are described herein.

Dependencies are inferred from the claim text.