Drugs that target topoisomerase action are effective anticancer agents and a number are FDA approved. There is a critical need for cell-based, tractable screening assays that facilitate detection of the next generation of anticancer drugs that specifically target topoisomerase enzymes. In this SBIR, the corporate sponsor (TopoGEN, Inc.) is proposing an innovative cell based screening method to identify new topoisomerase targeting agents. The approach is based on the idea that type II topoisomerases incite double strand DNA damage that is repaired by homologous recombination through accurate retrieval of genetic information from an undamaged DNA partner. A sophisticated genetic system has been devised in cancer cells based on a mutated reporter gene that is not expressed unless it becomes damaged by topoisomerase action under the influence of cytotoxic drugs. As a direct result, the reporter gene recombines leading to expression of the reporter. There are two milestones associated with this SBIR Phase I project. First, we will establish and test the genetic constructs that form the foundation of the screen. Second, we will design and reconstruct cell lines that allow implementation of the platform technology. A series of commercial kits and contract research products will be produced and beta tested, as part of this Phase I program. Clearly, the proposed research is relevant to that part of the NIH mission pertaining to developing and crafting new strategies to reduce the course of human disease.
Public Health Relevance: The development of targeted cancer therapies would be a clear advance in the treatment of cancer. Since cancer costs in the U.S. were nearly 1.4 million lives and $210 billion in 2005, it makes both medical and economic sense to invest in new pharmaceutical technologies. Smart drugs, which can selectively target and kill cancers, would begin to address this important public health issue.
Public Health Relevance Statement: Project narrative: The development of targeted cancer therapies would be a clear advance in the treatment of cancer. Since cancer costs in the U.S. were nearly 1.4 million lives and $210 billion in 2005, it makes both medical and economic sense to invest in new pharmaceutical technologies. Smart drugs, which can selectively target and kill cancers, would begin to address this important public health issue.
NIH Spending Category: Biotechnology; Cancer; Genetics; Human Genome
Project Terms: Accounting; Address; Affinity; Aging; Alleles; Allelomorphs; Animals; Anti-Cancer Agents; Anti-Oncogenes; Anti-Tumor Agents; Anti-Tumor Drugs; Antibodies; Antineoplastic Agents; Antineoplastic Drugs; Antineoplastics; Antioncogenes; Antiproliferative Agents; Antiproliferative Drugs; Assay; Bears; Binding Sites; Bioassay; Biochemical; Biochemistry; Biologic Assays; Biological; Biological Assay; Businesses; Cancer Drug; Cancer Genes; Cancer Treatment; Cancer cell line; Cancer-Promoting Gene; Cancers; Cell Line; Cell Lines, Strains; CellLine; Cells; Cellular Expansion; Cellular Growth; Centromere; Cessation of life; Chemistry, Biological; Chemotherapeutic Agents, Neoplastic Disease; Chromosomal Organization; Chromosomal Structure; Chromosome Organization; Chromosome Structures; Clone Cells; Combining Site; Communities; Contract Services; Custom; Cytotoxic agent; Cytotoxic drug; DNA; DNA Damage; DNA Double Strand Break; DNA Injury; DNA Recombination; DNA Sequence; DNA Topoisomerase (ATP-Hydrolysing); DNA Topoisomerase II; DNA Topoisomerases, Type II; DNA Type 2 Topoisomerase; DNA recombination (naturally occurring); DNA-Binding Proteins; DNA-Protein Interaction; Data; Data Banks; Data Bases; Databank, Electronic; Databanks; Database, Electronic; Databases; Death; Deoxyribonucleic Acid; Detection; Development; Diagnostics Research; Disease; Disorder; Double Strand Break Repair; Double-Stranded DNA; Drug Delivery; Drug Delivery Systems; Drug Industry; Drug Targeting; Drug Targetings; Drug usage; Drugs; EC 2.1.1; Elements; Emerogenes; Enzymes; Epigenetic; Epigenetic Change; Epigenetic Mechanism; Epigenetic Process; Event; FDA approved; FLR; Failure (biologic function); Foundations; Frequencies (time pattern); Frequency; GFP; Gene Conversion; Gene Inactivation; Gene Silencing; Gene Transcription; Generalized Growth; Generations; Genes; Genes, Cancer Suppressor; Genes, Onco-Suppressor; Genes, Reporter; Genetic; Genetic Alteration; Genetic Change; Genetic Recombination; Genetic Transcription; Genetic defect; Genetic screening method; Genome; Genome, Human; Genomics; Globin; Goals; Green Fluorescent Proteins; Growth; Hand; HeLa; Hela Cells; Hereditary; High Throughput Assay; Homologous Recombinational Repair; Human; Human Genome; Human, General; Hypermethylation; I-SceI; In Vitro; Industry; Industry, Pharmaceutic; Inherited; Instrumentation, Other; Intermediary Metabolism; International; Investigators; Ixodida; Killings; Knowledge; Libraries; Life; Link; METBL; Maintenance; Maintenances; Malignant Cell; Malignant Neoplasm Therapy; Malignant Neoplasm Treatment; Malignant Neoplasms; Malignant Tumor; Man (Taxonomy); Man, Modern; Marketing; Mediating; Medical Economics; Medication; Metabolic Processes; Metabolism; Methods; Methylation; Methyltransferase; Mission; Modeling; Molecular Genetic; Molecular Genetics; Mutate; Mutation; NIH; National Institutes of Health; National Institutes of Health (U.S.); Nature; Neoplasms; Nuclear Matrix; Nuclear Scaffold; Oncogenes; Oncogenes, Recessive; Oncogenes-Tumor Suppressors; Outcome; Pathway interactions; Pharmaceutic Preparations; Pharmaceutical Agent; Pharmaceutical Industry; Pharmaceutical Preparations; Pharmaceutical Technology; Pharmaceuticals; Pharmacologic Substance; Pharmacological Substance; Phase; Poisons; Position; Positioning Attribute; Probability; Process; Programs (PT); Programs [Publication Type]; Promoter; Promoters (Genetics); Promotor; Promotor (Genetics); Protein Methylation; Public Health; RNA Expression; Reactive Site; Reagent; Recombination; Recombination Repair; Recombination, Genetic; Regulation; Reporter; Reporter Genes; Research; Research Contracts; Research Personnel; Researchers; Retrieval; Right-On; SBIR; SBIRS (R43/44); SceI endonuclease; Scientist; Screening procedure; Senescence; Series; Services; Site; Small Business Innovation Research; Small Business Innovation Research Grant; Solubility; Somatic Cell; Specificity; Sum; System; System, LOINC Axis 4; Technology; Technology, Pharmaceutic; Technology, Pharmaceutical; Technology, Pharmacy; Testing; Ticks; Tissue Growth; Topo II; Topoisomerase; Topoisomerase II; Topoisomerase-II Inhibitor; Toxic Chemical; Toxic Substance; Transcription; Transcription, Genetic; Transforming Genes; Tumor Suppressing Genes; Tumor Suppressor Genes; Tumor Suppressor Proteins; Tumor-Specific Treatment Agents; Tumors; United States National Institutes of Health; Ursidae; Ursidae Family; Work; anticancer agent; anticancer drug; anticancer research; anticancer therapy; base; beneficiary; cancer cell; cancer research; cancer therapy; cell growth; clinical data repository; clinical data warehouse; cost; cultured cell line; data repository; design; designing; disease/disorder; drug development; drug discovery; drug use; drug/agent; ds-DNA; endo.SceI; endodeoxyribonuclease Sce I; endodeoxyribonuclease SceI; experience; experiment; experimental research; experimental study; failure; genetic testing; genome mutation; high throughput screening; homologous recombination; human disease; in vivo; inhibitor; inhibitor/antagonist; innovate; innovation; innovative; instrumentation; malignancy; meetings; meganuclease I-SceI; methylase; neoplasia; neoplasm/cancer; neoplastic growth; next generation; novel; oncosuppressor gene; ontogeny; p-Globin; pathway; poison; programs; protein expression; public health medicine (field); public health relevance; recombinational repair; reconstruction; relational database; repair; repaired; research study; screening; screenings; senescent; telomere; tool; toxic compound; transmethylase; tumor suppressor; uptake
