"Cancer progenitor cell markers" Phase I/II Fast-Track application In response to RFA-CA-08-011 "Innovative and Applied Molecular Analysis Technologies for Cancer (SBIR [R43/R44])" Circulating tumor cells (CTCs) have been identified in peripheral blood from patients with epithelial cancers. Recent studies suggest that CTCs could represent a potential alternative to biopsies as a source of tumor tissue for the detection, characterization and monitoring of non-hematologic cancers. However, current strategies for isolating CTCs are limited to complex analytic approaches based on epithelial cell surface markers. Since markers specific for cancer cells are lacking, the molecular identity of CTCs remains to be investigated. We postulate that the ability of cell adhesion matrix (CAM)-coated devices developed in Vitatex to isolate, characterize and propagate CTCs could lead to the identification of novel cancer stem or progenitor cell markers and expand the understanding of the mechanism of tumor progression and metastasis. To address this need, a panel of tumor progenitor cell markers upregulated in CTCs that were recently resolved by this team will be used to improve the CTC detection specificity and sensitivity in patients with epithelial ovarian cancer, as well as to evaluate the potential role of CTCs in ovarian tumor peritoneal metastasis. Initially we will select novel tumor progenitor and invasiveness markers and optimize a cell-based flow cytometry blood test by validating its performance using fluorescence microscopic imaging to improve the sensitivity and specificity of CTC detection. We will then develop a nucleic acid-based blood test using a focused panel of tumor progenitor cell markers in multigene quantitative PCR analysis to phenotype patients with ovarian cancer who are treated at the Stony Brook University Medical Center and to monitor treatment response. To evaluate the relevance of CTCs in metastatic progression, cells sorted by both CAM adhesion and expression of a tumor progenitor gene will be examined for their ability to progress into peritoneal, liver and lung metastases by using an experimental ovarian metastasis animal model. The commercialization objectives are to manufacture an efficient rare cell separation system as a research tool for molecular analysis of epithelial cancers in peripheral blood, and to develop a novel blood test product that allows more sensitive diagnostic and prognostic evaluation of cancer, particularly relating to its metastatic potential.
Public Health Relevance Statement: Project Narrative The proposal is designed to generate effective methods and devices for the isolation of cancer cells from blood for molecular analysis of ovarian cancer, and to develop a novel blood test product that allows more sensitive diagnostic and prognostic evaluation of cancer, particularly relating to its metastatic potential.
Project Terms: Academic Medical Centers; Address; Adhesions; Affect; Affinity; Animal Model; Animal Models and Related Studies; Antibodies; Assay; Benign; Bioassay; Biologic Assays; Biological Assay; Biopsy; Blood; Blood Cells; Blood Sample; Blood Tests; Blood specimen; Cancer Patient; Cancer of the Ovary; Cancer stem cell; Cancers; Cell Attachment; Cell Function; Cell Isolation; Cell Process; Cell Segregation; Cell Separation; Cell Separation Technology; Cell physiology; Cell surface; Cell-Matrix Adhesions; Cell-Matrix Junction; Cells; Cellular Function; Cellular Physiology; Cellular Process; Clinical Research; Clinical Study; Complex; Cytofluorometry, Flow; Detection; Development; Devices; Diagnostic; Disease; Disease-Free Survival; Disorder; Drug resistance; Epithelial; Epithelial Cells; Epithelial ovarian cancer; Evaluation; Event-Free Survival; Exhibits; Extravasation; Flow Cytofluorometries; Flow Cytometry; Flow Microfluorimetry; Fluorescence; Gene Expression; Gene Expression Microarray Analysis; Generalized Growth; Genes; Goals; Greater sac of peritoneum; Growth; Hematologic Tests; Hematological Tests; Hematology Testing; IVM; Image; Individual; Institution; Investigation; Knowledge; Lead; Leakage; Liver; Lung; Magnetism; Malignant Cell; Malignant Neoplasms; Malignant Ovarian Neoplasm; Malignant Ovarian Tumor; Malignant Tumor; Malignant Tumor of the Ovary; Malignant neoplasm of ovary; Mammals, Mice; Measurement; Metastasis; Metastasis to Ovary; Metastasize; Metastatic Malignant Neoplasm to the Ovary; Metastatic Malignant Tumor to the Ovary; Metastatic Neoplasm; Metastatic Tumor; Methods; Mice; Microfluorometry, Flow; Microscopic; Molecular; Molecular Analysis; Monitor; Mother Cells; Murine; Mus; Neoplasm Metastasis; Non-Hematologic Cancer; Non-Hematologic Malignancy; Normal Cell; Nucleic Acids; Operation; Operative Procedures; Operative Surgical Procedures; Ovarian Metastasis; Ovarian Tumor; Ovary Neoplasms; Patients; Pb element; Performance; Peripheral Blood Cell; Peritoneal; Peritoneal Cavity; Phase; Phenotype; Population; Post-Transcriptional Gene Silencing; Post-Transcriptional Gene Silencings; Posttranscriptional Gene Silencing; Posttranscriptional Gene Silencings; Progenitor Cells; Quelling; RNA Interference; RNA Silencing; RNA Silencings; RNAi; Recurrence; Recurrent; Reporting; Research; Respiratory System, Lung; Reticuloendothelial System, Blood; Role; SBIR; SBIRS (R43/44); SCID; Sampling; Secondary Neoplasm; Secondary Tumor; Sensitivity and Specificity; Sequence-Specific Posttranscriptional Gene Silencing; Severe Combined Immunodeficiency; Severe Combined Immunodeficiency Syndrome; Severe Combined Immunologic Deficiency; Small Business Innovation Research; Small Business Innovation Research Grant; Sorting - Cell Movement; Source; Spillage; Stem cells; Subcellular Process; Surgical; Surgical Interventions; Surgical Procedure; System; System, LOINC Axis 4; Technology; Testing; Time; Tissue Growth; Tumor Cell; Tumor Cell Invasion; Tumor Cell Migration; Tumor Invasion; Tumor Tissue; Tumor of the Ovary; University Medical Centers; Validation; Woman; base; body system, hepatic; cancer cell; cancer metastasis; cancer progression; cell sorting; cell type; chemotherapy; clinical applicability; clinical application; combined T and B cell inborn immunodeficiency; commercialization; design; designing; disease/disorder; drug resistant; flow cytophotometry; heavy metal Pb; heavy metal lead; imaging; improved; in vivo; innovate; innovation; innovative; intravital microscopy; magnetic; malignancy; model organism; neoplasm progression; neoplasm/cancer; neoplastic cell; neoplastic progression; nonhematologic cancer; novel; ontogeny; organ system, hepatic; ovarian cancer; ovarian neoplasm; particle; peripheral blood; progenitor; prognostic; pulmonary; resistance to Drug; resistant to Drug; response; social role; sorting; stem; surgery; tool; treatment response; tumor; tumor progression
