SBIR-STTR Award

The detection and enumeration of circulating tumor cells (CTC) has the potential to become a very powerful tool in cancer diagnosis and treatment. However, current technologies for CTC detection are not yet established in routine clinical practice. One primary reason is that CTCs present in body fluids at extremely low concentrations of 1 in 1 million or more normal hetergeneous cells. Existing technologies lack the sensitivity and specificity required for reliable and reproducible detection of these rare CTCs. Another reason is that current technology does not distinguish well the "live" from "dead" or "dying" CTCs. The overall goal of this research application is to develop an assay technology named QMAGEX for Quantitative Multiplex Analysis of Gene Expression in Single Cells in Suspension and to utilize the technology for sensitive detection, accurate enumeration, and functional analysis of CTCs in body fluids. The long-term goal of this effort is to leverage this assay technology to develop a suite of high value cancer diagnostic products. These products would satisfy many significant unmet needs in cancer diagnosis, especially in the areas of early detection, therapy guidance, and recurrence monitoring. The research effort described in this Phase I SBIR application represents the first, "proof-of-concept" step towards the long-term goal. Well characterized breast and prostate cancer cell lines will be used as a model system and detection and enumeration of CTC at a clinically useful concentration (one CTC in every 10,000 normal white blood cells) will be demonstrated. If successful, Phase II effort will be aimed at developing high information content QMAGEX assay for detection of CTC at a concentration below one in 1 to 10 million normal white blood cells. The assay will be tested in real clinical blood or bone marrow samples and their clinical utility evaluated. Commercial diagnostic products focusing on specific cancers and specific diagnostic applications will be developed in Phase III

The detection and enumeration of circulating tumor cells (CTCs) has the potential to become a very powerful tool in cancer diagnosis and treatment. However, current technologies for CTC detection are not yet established in routine clinical practice. One reason is that CTCs are present in blood at an extremely low concentration of one in 10 million white blood cells. Existing technologies lack the sensitivity and/or specificity required for reliable detection of these rare CTCs. Another reason is that current technology does not offer information about the molecular status of CTCs. The overall goal of this project is to develop an assay technology named QMAGEX for Quantitative Multiplex Analysis of Gene Expression in Single Cells and to utilize the technology for sensitive detection, accurate enumeration, and functional analysis of CTCs in body fluids. The long-term goal of this effort is to leverage this assay technology to develop a suite of high value cancer diagnostic products. These products would satisfy many significant unmet needs in cancer diagnostics, especially in the area of early detection, therapy guidance and recurrence monitoring. In Phase I, we have developed a prototype QMAGEX assay, demonstrated its capability for detecting RNA transcripts in situ in individual cells with single copy sensitivity, and proven its feasibility for cancer cell detection in blood. In Phase II, we aim to move QMAGEX from the current proof-of-concept stage to a robust and high information content assay. The specific aims in Phase II include: 1) Develop essential components for high information content 4-plex QMAGEX assay; 2) Develop and validate a flow cytometric 4-plex QMAGEX assay for rare cell detection in blood; and 3) Evaluate the clinical utility of the high information content 4-plex QMAGEX assay for detection of CTCs in metastatic breast cancer patients. Commercial diagnostic products focusing on specific cancers and specific diagnostic applications will be developed in Phase III.

Public Health Relevance:
It has been known that circulating tumor cells (CTCs) can provide an early indication of tumor growth and metastasis. Thus, detection and molecular analysis of CTC using the QMAGEX assay system will be valuable in early detection of cancer, in identifying cancer patients for targeted therapies and determining response to treatment, in monitoring cancer progression and recurrence.

Public Health Relevance:
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