Functional lipidomics: Lysophosphatidic acid as a target for molecular diagnosis and therapy of ovarian cancer

Epithelial ovarian cancer has the highest mortality rate of all gynecologic malignancies owing to late diagnosis and a lack of effective tumor-specific therapeutics. Ovarian carcinogenesis and metastasis occurs as a consequence of an orchestrated cascade of genetic, molecular, and biochemical events. Indeed, over the last several years, an extensive array of aberrations have been identified in this tumor; however, their roles in the pathophysiology of ovarian cancer remain to be elucidated. Abnormal lysophosphatidic acid (LPA) production, receptor expression, and signaling are frequently found in ovarian cancers, suggesting that LPA plays a role in the pathophysiology of the disease. Although LPA is the simplest lipid found in nature, it contains a number of structure components providing important informational content. High-affinity LPA receptors of the G-protein-coupled receptor family provide evidence for the importance of the molecule in normal cellular functions. LPA levels and the levels of related lysopholipids have been reported to be elevated in patient fluids including ascitic fluid and peripheral blood. The recent identification of the enzymes that mediate the degradation and production of LPA and the development of receptor-selective analogs may lead to new approaches in the treatment of this deadly disease. The LPA pathway may contain novel molecular targets, illustrating the potential role of functional lipidomics in the development of new therapeutic and diagnostic strategies for disease management.