CTC Screening Assay to Address Health Disparities in Women with Ovarian Cancer

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 DESCRIPTION (provided by applicant): Epithelial Ovarian Cancer (EOC) is the 5th leading cause of cancer-related deaths among women in the US and is the leading gynecological cancer killer with ~22,000 cases reported in 2014. EOC has been called a "silent killer" because most women (>70%) are diagnosed at late stages of disease due to a lack of clinically sensitive and specific screening test and a lack of symptoms until late stage disease onset. While the incidence rate of EOC in the US is highest among white females, there exists a dramatic disparity in post-diagnosis outcomes in other populations with African-American women exhibiting substantially greater mortality based on 5-year survival rates. A combination of insufficient early detection strategies as well as reduced access to surgical treatment (required at later stages of disease) appears to contribute to the disparity. Improved access to advanced screening assays, and thereby earlier detection, is therefore urgently needed to improve outcomes, particularly in disparately effected populations. Analysis of circulating tumor cells (CTCs) from cancer patients' blood have demonstrated prognostic value in metastatic cancers (1) (1)(1)but the use of CTCs for diagnosing early stage disease requires a degree of sensitivity and specificity currently unavailable in existing CTC analysis technologies. An innovative CTC detection technology will emanate from this SBIR research project that will have unique capabilities suited to the early detection of EOC and potentially other cancers as well. The technology uses low-cost, disposable, plastic CTC fluidic cartridge that possess the ability to select CTCs directly from whole blood with extremely high recoveries (>90%), unprecedented purities (>85%) and can enumerate the captured CTCs using a label-less approach with a simple single-cell transducer (micro-CTC Coulter Counter, µC3). The technology provides a simple workflow with full process automation, ideal for a screening test that can be utilized within resource-limited settings. The technology will process whole blood directly (~2 mL input) and affinity select the CTCs, release the CTCs from the capture surface and count them using an on-chip µC3. Unique to our platform is the ability to select different CTCs subpopulations from a single sample. BioFluidica has tested its capture system using a novel CTC-isolation antigen, which, as the preliminary data indicates, is more prevalent in early stage disease compared to the more commonly used selection target, epithelial cell adhesion molecule (EpCAM). The ability to capture multiple stage-specific CTC subpopulations has the potential to diagnose patients at early stages of disease as well as assess treatment efficacy and the potential for disease recurrence. The goal of this proposal is to initiate the development of a powerful EOC screening test, accelerating treatment and improving currently poor prognoses, especially in disparately affected African-American women. Successful completion of this Phase I program will provide the impetus to move the technology into early detection scenarios for other cancers that show disparities, such as breast cancer in African-American women.