LYSOPHOSPHOLIPID RECEPTORS AS TARGETS FOR CANCER THERAPY

The ultimate goal of the proposed research is to identify effective therapeutic agents for cancer, using specific lysophospholipid receptors as the cellular targets. Ceretak, LLC is particularly interested in a family of cell surface G-proteins (GPCR) that are activated by lysophosphatidic acid (LPA). The focus of this proposal is on LPA receptors, also known as Edg ( for Endothelial differentiation gene) receptors, and the development of tools to identify lead compounds that selectively modulate biological responses, including chemotactic and proliferative markers, in response to LPA. The specific aims of this proposal are (a) to use stable cell lines expressing Edg-2 and Edg-7 receptors to screen our in-house chemical library, (b) to characterize compounds with demonstrated activity against one or more of these receptors in relevant in vitro assays using stably transfected cell lines, as well as selected tumor cell lines, known to express specific LPA receptors, and (c) to expand the patient sample size in our initial cancer profiling array studies to support the current findings that certain LPA receptors undergo significant alterations in their expressed pattern in malignant states.