Arrayit Corporation (ARYC)

[MikeCr]

Biomarkers in Medicine
June 2010
The dire need to develop a clinically validated screening method for the detection of early-stage ovarian cancer
Ny Sonia Dutta?, Feng-qiang Wang? and David A Fishman

For almost half a century, the WHO has urged the medical community to create screening methods with the primary purpose of detecting disease at an early, treatable stage [1]. This is of particular importance in epithelial ovarian cancer (EOC) given that there are no clinically validated biomarkers or screening protocols available..........

Full text:
http://www.futuremedicine.com/doi/full/10.2217/bmm.10.54

Some excerpts:

"Given ovarian cancer’s relatively low general population incidence rate (1.8%) [2], a valid screening test must have both a high sensitivity and a high specificity to decrease the number of false-positive test results and the subsequent invasive surgical procedures undoubtedly associated with this result. The ideal screening test for the postmenopausal population (with a prevalence of one in 2500) would require a specificity of 99.6% to yield an approximate positive predictive value of 10%, where a surgeon performs ten operations for each case of ovarian cancer detected. The positive predictive value of most screening tests is determined by specificity and disease incidence – given ovarian cancer’s low frequency, achieving an acceptable positive predictive value requires an extremely high specificity, especially in average-risk populations."

"Multiple initiatives have been undertaken to discover strategies that detect and diagnose early-stage EOC, including the search for novel serum biomarkers and the development of new technologies, such as contrast-enhanced ultrasonography, with a number of them demonstrating hopeful results. The ideal screening test for ovarian cancer would be a simple measurement of biomolecules in bodily fluids, such as blood, serum or urine, whose absolute concentrations could differentiate cancer from noncancer and be organ specific. In the last decade, insights into the EOC microenvironment, as well as technological advances, such as microarrays and proteomics, have triggered the discovery of hundreds of potential clinically valuable biomarkers:

? Lysophosphatidic acid (LPA)... (description follows)
? Human epididymal protein (HE)...(description follows)
? Osteopontin (OPN)... (description follows)
? Kallikreins (KLKs)... (description follows)
? Claudins )... (description follows)

In addition to the biomolecules mentioned previously, patient-derived tumor-reactive antibodies are also considered to be new diagnostic markers.....

Of particular note, traditional genetic pedigree analysis of ovarian cancer patients may provide information to help identify high-risk populations;....

Despite these advances, at present, no clinically validated screening protocol for the detection of early-stage EOC exists. The discovery of novel biomarkers relies on obtaining a better understanding of the initiation and progression of EOC. Clinical validation and implementation of biomarkers will also benefit from advancements in new molecular and imaging technologies as patient care is optimized. Fortunately, hundreds of biomarkers have been identified; however, their clinical utility remains to be determined. In addition, the enhanced imaging capabilities of the ovary by ultrasound are providing practitioners with the ability to more accurately and precisely identify changes specific to the newly transformed ovary. The combination of these two modalities, biomarker panels and biologically based imaging may be the future. Therefore, we must forge ahead to develop a validated early-detection protocol that will not only decrease the number of advanced-stage diagnoses and deaths attributed to ovarian cancer but, most importantly, positively impact the future of women’s healthcare.