Rapid, Multiplexed Biosensor for Non-Invasive Detection of Gene Mutations and Personalization of Therapy in Non-Small Cell Lung Cancer There is an urgent need for improved blood-based liquid biopsies to aid the detection circulating tumor DNA (ctDNA). Such assays will be revolutionary for guiding cancer treatment because ctDNA is a very specific cancer biomarker that can be collected non-invasively, thus addressing the challenges of traditional invasive tissue biopsies. Detection of ctDNA is challenging because these biomarkers exist at trace concentrations and are vastly outnumbered by background wild type DNA. Giner, Inc. proposes to develop an electrochemical detection method for rapid, sensitive, and selective detection of single-base mutations in the EGFR gene associated with sensitivity to the tyrosine kinase inhibitor (TKI) class of drugs in non-small cell lung cancer (NSCLC). The developed assay will be adapted for multiplexed ctDNA detection, validated with lung cancer patient plasma samples, and integrated into a prototype microfluidic device, thus achieving a significant milestone toward regulatory evaluation. This technology will help increase access of personalized therapies to NSCLC patients for better treatment outcomes, and offer a compelling competitive advantage over gold standard digital PCR tests in terms of lower cost, minimized sample preparation requirements, increased multiplexed detection, and a much faster sample-to-answer turnaround time.
Public Health Relevance Statement: PROJECT NARRATIVE The goal of this program is to develop a rapid, easy, and low cost electrochemical sensor for non-invasive detection of cancer-specific, gene mutation biomarkers in plasma of lung cancer patients. Detection of these biomarkers will help guide the use of targeted cancer therapies for better outcomes in patients with advanced stage lung cancer, when invasive tissue biopsies are difficult or impossible to obtain.
Project Terms: Adoption; Alkynes; Archives; Azides; Biological Assay; Biologic Assays; Bioassay; Assay; Biopsy; Blood; Blood Reticuloendothelial System; Malignant Neoplasms; neoplasm/cancer; malignancy; Malignant Tumor; Cancers; Non-Small-Cell Lung Carcinoma; nonsmall cell lung cancer; Nonsmall Cell Lung Carcinoma; Non-Small Cell Lung Cancer; NSCLC - Non-Small Cell Lung Cancer; NSCLC; cultured cell line; Strains Cell Lines; CellLine; Cell Line; Death; Cessation of life; Diagnosis; Disorder; Disease; Deoxyribonucleic Acid; DNA; DNA Hybridization Probes; DNA Probes; resistant to Drug; resistance to Drug; drug resistant; Drug resistance; drug/agent; Pharmaceutic Preparations; Medication; Drugs; Pharmaceutical Preparations; Enzyme Gene; Enzymes; Exons; allelic frequency; Allele Frequency; Gene Frequency; Genotype; Goals; Gold; Head; Modern Man; Human; Hybrids; Institutes; Laboratory Research; Closure by Ligation; Ligation; Medical Device; men's; men; Methods; DNA Molecular Biology; Molecular Biology; genome mutation; Genetic defect; Genetic Change; Genetic Alteration; Mutation; oxidation reduction reaction; Redox; Oxidation-Reduction; Patients; Reticuloendothelial System, Serum, Plasma; Plasma Serum; Blood Plasma; Plasma; proto-oncogene protein c-erbB-1; erbBl; erbB-1 Proto-Oncogene Protein; erbB-1; c-erbB-1 Protein; c-erbB-1; Urogastrone Receptor; Transforming Growth Factor alpha Receptor; TGF-alpha Receptor; HER1; Epidermal Growth Factor-Urogastrone Receptors; Epidermal Growth Factor Receptor Protein-Tyrosine Kinase; Epidermal Growth Factor Receptor Kinase; ERBB Protein; EGFR; EGF Receptor; Epidermal Growth Factor Receptor; R&D; R & D; Development and Research; research and development; Sensitivity and Specificity; biological signal transduction; Signaling; Signal Transduction Systems; Intracellular Communication and Signaling; Cell Signaling; Cell Communication and Signaling; Signal Transduction; Specificity; Technology; Testing; Time; Body Tissues; Tissues; United States; Woman; Measures; Treatment outcome; Device Designs; Mediating; Custom; base; sensor; improved; Clinical; Phase; DNA Primers; Oligodeoxyribonucleotide Primers; Chemicals; Evaluation; Training; Malignant neoplasm of lung; lung cancer; Pulmonary malignant Neoplasm; Pulmonary Cancer; Malignant Tumor of the Lung; Disease Progression; Oncologist; Collaborations; Reporter; Diagnostic; programs; Hour; Reaction; Techniques; System; Test Result; Tumor Tissue; Benchmarking; Best Practice Analysis; American; Early Diagnosis; early detection; experience; Gene Mutation; Gene Alteration; mutant; Performance; cycloaddition; technology development; tech development; Biosensor; biological sensor; DNA amplification; Categories; Devices; Reporting; Positioning Attribute; Position; Chest; Thorax; Thoracic; Thorace; Modeling; Sampling; rapid technique; rapid method; Intervention; interventional strategy; Intervention Strategies; cancer therapy; anticancer therapy; anti-cancer therapy; Malignant Neoplasm Treatment; Malignant Neoplasm Therapy; Cancer Treatment; Manufacturer Name; Manufacturer; Pharmacological Substance; Pharmaceuticals; Pharmaceutical Agent; Pharmacologic Substance; µfluidic; Microfluidics; TK Inhibitors; Protein Tyrosine Kinase Inhibitors; PTK Inhibitors; Tyrosine Kinase Inhibitor; EGFR gene; c-erbB-1 Proto-Oncogenes; c-erbB-1 Gene; Epidermal Growth Factor Receptor Genes; ERBB1 Gene; ERBB1; ERBB; Address; Microfluidic Microchips; microfluidic chip; Microfluidic Lab-On-A-Chip; Microfluidic Device; Detection; Cancer Etiology; Cancer Cause; Cancer Gene Mutation; cancer specific gene mutation; Cancer Patient; Non-Invasive Cancer Detection; Noninvasive Detection; Noninvasive Cancer Detection; Non-Invasive Detection; Small Business Innovation Research Grant; Small Business Innovation Research; SBIR; Translational Research; translation research; Translational Science; Validation; Preparation; Process; point of care; pre-clinical; preclinical; cost; digital; multiplex detection; design; designing; Outcome; Consumption; Resistance; resistant; clinical application; clinical applicability; Early treatment; early therapy; prototype; commercialization; tumor; clinical care; FDA approved; treatment response; therapeutic response; response to treatment; Biological Markers; biomarker; biologic marker; bio-markers; resistance mutation; resistant mutation; Secure; personalized medicine; personalized treatment; personalized therapy; personalization of treatment; targeted treatment; targeted therapy; targeted therapeutic agents; targeted therapeutic; targeted drug treatments; targeted drug therapy; targeted cancer therapy; tumor DNA; tumor-specific DNA; tumor cell DNA; clinically actionable; cancer biomarkers; cancer markers; liquid biopsy; clinical diagnostics; sensor technology; sensing technology
