The rise in using companion diagnostics to guide selection of pharmacological agents in cancer treatment has led to a need for technologies which can extend these diagnostics to additional patients with difficult to access tumors. Such diagnostic assays are performed on cells extracted from tumors or metastatic cells found distant from the primary tumor site. Evaluation of bodily fluids, including blood, urine, effusions, for disseminated malignant cells originating from the lung, breast or other organs is an alternative to examination of primary tumor tissue, especially when biopsy is not possible at the primary tumor site. For example, pleural effusions, which can be the first presentation of a patient's cancer and thus contain some of the most diagnostically relevant cells, could be used as an easily accessible source of malignant cells to assay specific genetic lesions indicative of susceptibility to targeted therapies. However, the accuracy of these assays is limited by the presence of a large background of normal cells. Current approaches for enriching malignant cells from bodily fluids for these assays can require prior knowledge about the type of malignancy, which is often unavailable, or result in insufficient purity (<40%) for confident diagnoses. Biophysical properties of cells have been shown to be extremely specific label-free biomarkers of malignant phenotypes. Here, we aim to develop an instrument which will isolate target cancer cells using a combination of intrinsic physical biomarkers associated with malignancy - cell size and deformability - with high yield and purity. CytoVale is commercializing a technology, 'deformability cytometry', which assays the biophysical properties of thousands of cells per second and has demonstrated utility in diagnosing malignancy in pleural effusions. Expanding upon its core technology, CytoVale will, in this project, develop an instrument which will be able to isolate malignant cells for companion diagnostic assays, from large volumes of bodily fluids, with higher sensitivity and specificity than currently available techniques. This wil increase the accessibility of these powerful assays which have demonstrated immense clinical success in recent years, thereby improving patient outcomes.
Public Health Relevance Statement: Public Health Relevance: Determining whether a patient's cancer will respond to new cancer drugs requires access to tumor cells and genetic testing. For many patients this is not possible because of prior resection of the primary tumor, micrometastases being too small to biopsy, or the proximity of tumor nodules to critical physiological sites. We are developing a simple microtechnology that uses the physical properties of cancer cells to concentrate and enrich these cells from more accessible bodily fluids and enable accurate genetic testing.
NIH Spending Category: Bioengineering; Cancer
Project Terms: Antigens; Antineoplastic Agents; base; Benign; Biological Assay; Biological Markers; Biomechanics; biophysical properties; Biopsy; Blood; Blood Cells; Breast; Caliber; cancer cell; Cancer cell line; Cancer Patient; cancer therapy; Cell Extracts; Cell Line; Cell Separation; Cell Size; Cell surface; Cells; Clinical; Clinical Research; companion diagnostics; Companions; cost; Cytometry; Data; design; Detection; Diagnosis; Diagnostic; diagnostic assay; Diagnostic tests; Distant; effusion; Evaluation; Excision; Fractionation; Gene Mutation; Genetic; Genetic screening method; Goals; Health; improved; Injection of therapeutic agent; instrument; interest; Knowledge; Label; Lesion; Leukocytes; Liquid substance; Lung; Malignant Neoplasms; malignant phenotype; Masks; Measures; Mechanics; meetings; Mesothelial Cell; Methods; Microfluidics; Micrometastasis; Modeling; Molds; Molecular; Mutation; neoplastic cell; Nodule; Normal Cell; Organ; Outcome; particle; Patients; Peritoneal Fluid; Pharmaceutical Preparations; Pharmacotherapy; Phase; physical property; Physiological; Pleural; Pleural cavity; Pleural effusion disorder; Point Mutation; Population; Population Distributions; Predisposition; Primary Neoplasm; Property; Reporting; Resistance; Sampling; Science; Sensitivity and Specificity; Shapes; Signal Transduction; Site; Solutions; Sorting - Cell Movement; Source; Specimen; Stress; Stretching; success; System; targeted treatment; Techniques; Technology; translational medicine; tumor; Tumor Tissue; tumorigenic; Urine
