[Lysophosphatidic acid as a potential target for treatment and molecular diagnosis of epithelial ovarian cancers].
Ovarian carcinoma 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 is accompanied by a complicated cascade of genetic, molecular, and biochemical events. 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. Moreover, the LPA pathway may provide novel molecular targets, illustrating how the development of new therapeutic and diagnostic strategies can contribute to disease management. The recent identification of the metabolizing enzymes that mediate the degradation and production of LPA and the development of receptor selective-analogues open a potential new approach to the treatment of this deadly disease. In this review, it is clearly presented that aberrations of LPP production contribute to the progression of ovarian cancer, just us overexpression of these metabolizing enzymes return the physiologic situation and inhibit the growth of the cancer cells. LPPs exert their effect through metabolizing extracellular LPA. This also clearly explains the dominant "bystander effect" of these enzymes. LPA through its production, metabolism, and receptors may provide an excellent target for the development of molecular therapeutics, and the early detection of molecular forms of LPA, other lysolipids, and the activities of LPA pathway receptors and enzymes may facilitate both diagnosis and monitoring the response of a given patient to therapy. The impressive development of knowledge about the pathway regulating LPA production and the identification of selective LPA-receptor agonists suggest that targeting the LPA cascade could be a real addition to the management and treatment of this still-deadly disease. Additional studies of the LPA cascade and other phospholipids in ovarian cancer are essential to further elucidate their critical roles.
Tanyi
János
J
Department of Gynecologic Oncology, University of Pennsylvania Health System, Philadelphia, USA.
Rigó
János
J
D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008246:Lysophospholipids / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors
D014408:Biomarkers, Tumor; D008246:Lysophospholipids; D012333:RNA, Messenger; D049368:Receptors, Lysophosphatidic Acid; C032881:lysophosphatidic acid