LPA Sensor for Early-Stage Ovarian Cancer Detection

DESCRIPTION (provided by applicant): Women with ovarian cancer have the highest mortality rate among women with gynecological cancers. It is estimated that there will be over 16,090 deaths from ovarian cancer in the US in 2004. The high mortality rate is related to the inability of detecting ovarian cancer in the early stages of the disease. Over 60% of women have widespread metastatic disease at initial diagnosis. If the disease is diagnosed and treated while the cancer is still limited to the ovary (Stage I), the cure rate is greater than 90%. However, only 29% of all ovarian cancers are diagnosed in this early stage. Ovarian cancer must be detected early to overcome this staggering mortality rate. Currently, the only definitive test for ovarian cancer is an invasive laparoscopic procedure. Due to the simplicity of a blood test, the analysis for cancer markers is an appealing method currently under investigation as an alternative, non-invasive, screening test for ovarian cancer. A potential cancer marker for ovarian cancer is the phospholipid lysophosphatidic acid (LPA). Studies have shown that LPA, a naturally occurring phospholipid, is found in high levels in the plasma and ascetic fluid of ovarian cancer patients. A simple method to detect this important lipid does not exist and could potentially save thousands of lives. The most common technique for quantifying this molecule is mass spectrometry (MS). Typically MS requires expensive equipment to perform. The aim of this Phase I proposal is to develop a simple and inexpensive sensor for LPA. The technology is based on an optical sensor that is sensitive to nanoscale conformational changes of an LPA specific receptor protein that is tethered to a surface. LPA present in samples will selectively bind to the tethered receptor which will undergo a conformational change. This will produce a change in optical signal of a simple reflected laser beam onto a CCD detector. The tethered molecules are arranged on the surface in a pattern and hence, the optical signal is the diffraction pattern of the reflected laser beam. The technology will be LPA specific but is easily adaptable to other lipids, proteins, and a wide range of molecules. The main goals of this proposed research is to prepare a tethered LPA receptor, assemble the sensing device, and provide a first generation breadboard device. The criteria for success of this proposed research is LPA detection on biologically relevant samples by the end of the proposed research.