KOSEN 한인과학기술자네트워크

Cancer Treatment and Diagnosis Primary Sponsor: Department of Health and Human Services Deadline: 4/1/2001; 8/1/2001; 12/1/2001 KEYWORDS Cancer Diagnosis. The Cancer Diagnosis Program (CDP) supports the development of technologies, reagents, instrumentation, and methodologies to improve cancer diagnosis or prognosis or to predict or assess response to therapy. This does not include technologies for imaging of patients. CDP also supports the adaptation or improvement of basic research technologies for use as clinical tools. Technologies supported by CDP may be designed to work with tissues, blood, serum, urine, or other biological fluids. Technologies supported by CDP include but are not limited to the following: 1. Technologies for comprehensive and/or high throughput analysis of molecular alterations at the level of DNA, RNA, or protein. Includes for example, mutation detection systems, gene expression arrays, high throughput proteomics (including post-translational modification and protein-protein interactions and methods for protein quantitation). 2. Micro-electro mechanical systems (MEMs) for the analysis of DNA, RNA, or protein (e.g., microcapillary systems, lab on a chip applications, microseparation technologies). 3. Mass spectrometry for the analysis of nucleic acids or proteins. 4. Discovery and development of new or improved diagnostic markers or probes targeting changes in DNA, RNA, or proteins, including the generation of molecular diversity libraries by phage display and other combinatorial techniques, and affinity-based screening methods. 5. cDNA library technologies, including improved methods for generating high quality cDNA clones and libraries and methods for generating high quality cDNA from tissues (including archived specimens). 6. Resources for clinical research. a. Instruments, technologies or reagents for improved collection, preparation, and storage of human tissue specimens and biological fluids. b. Improved methods for isolation and storage of DNA, RNA, or proteins. c. Tissue and reagent standards: development of standard reagents such as representational DNA, RNA, and proteins and standard tissue preparations to improve the quality of or facilitate the validation of clinical laboratory assays. d. Methodologies for directed micro-sampling of human tissue specimens, including for example, new or improved methodologies for tissue microarrays. 7. Tissue preservation: fixatives and embedding materials or stabilizers that preserves tissue integrity and cellular architecture and simultaneously allows molecular analysis of DNA, RNA, or proteins. 8. Bioinformatics a. Methods for acquisition and analysis of data associated with molecular profiling and other comprehensive molecular analysis technologies, including for example, analysis of microarray images and data as well as methods to combine, store and analyze molecular data produced by different techniques (e.g. combined analysis of proteomics and gene expression data). b. Methods for collecting, categorizing or analyzing large data sets containing pathology data or histological images and associated clinical or experimental data, including for example, tumor marker measurements, tissue microarray data, and other relevant biological information. c. Software/algorithms to interpret and analyze clinical and pathology data including methods that relate data from clinical databases to external data sources. Includes for example, neural networks, artificial intelligence, data-mining, data-trend analysis, patient record encryption protocols, and automatic diagnostic coding using standard nomeclatures. d. Informatics tools to support tissue procurement and tissue banking activities. 9. Statistical methods and packages designed for data analysis including correlation of clinical and experimental data. 10. Automated Cytology a. High resolution image analysis for use with specimens (e.g., blood, tissues, cells) and tissue microarrays. b. Instrumentation including microscopy and flow cytometry. c. CGH, FISH, immunohistochemical staining and other hybridization assays using probes with fluorescent or other novel tags. d. Methods for single cell isolation and sorting. e. Methods for single cell classification and analysis. 11. Instrumentation for the detection and diagnosis of tumors, including endoscopy and magnetic resonance spectroscopy (MRS). 12. Immunoassays using monoclonal, polyclonal, or modified antibodies. Affinity-based binding assays using libraries of aptamers including chemical ligands, small peptides or modified antibodies. For additional information about areas of interest to the CDP Technology Development Branch, visit our home page at: http://www-cdp.ims.nci.nih.gov/tdb.html. B. Biochemistry and Pharmacology. Preclinical studies designed to improve cancer treatment in the following areas: Discovery of new drugs and treatment strategies, selective targeting, development of new preclinical models, pharmaceutical development, and toxicologic evaluations. Emphasis is on molecular targeted approaches. In addition to the topics below, Biochemistry and Pharmacology sponsors special initiatives for Small Business Innovation Research (SBIR) and Small Technology Transfer Research (STTR) programs. For additional information, please visit our home page at http://dtp.nci.nih.gov and select "Funding." 1. Drug Discovery a. Design and synthesize novel compounds for evaluation as potential anticancer agents. Synthesize simpler analogs of complex antitumor structures that retain antitumor activity. b. Develop computer modeling and biophysical techniques such as x-ray crystallography and NMR spectroscopy. c. Design prodrugs of anticancer agents that are selectively activated in cancer cells. d. Discover new anticancer agents aimed at relevant targets that exploit unique properties of tumors, that induce or modulate apoptosis, or that induce or modulate differentiation. e. Design and synthesize anticancer prodrugs, latent drugs, or modifiers of cancer drug metabolism or excretion. f. Develop ways to produce adequate quantities of promising natural products or natural product derivatives through total synthesis. g. Develop scale-up technology for the synthesis of materials with promising anticancer potential. h. Develop chemical libraries for anticancer drug screening programs. The generation of small molecular weight libraries (<700 MW, e.g., non-polymeric organic molecules, transition-state analogs, cyclic peptides, peptidomimics) is encouraged. i. Develop array technologies for drug discovery. 2. Drug Evaluation a. Develop and evaluate anti-metastatic and/or anti-angiogenesis agents or strategies in appropriate model systems. b. Develop and evaluate anticancer gene therapy in appropriate model systems. The development of new gene delivery approaches is encouraged. c. Develop novel or improved in vitro and in vivo test systems. There is a special need for new types of in vivo tumor models, such as orthotopic tumor models, models using transgenic or knockout animals, models for AIDS-associated malignancies, and models to evaluate agents that induce differentiation or apoptosis. d. Develop and evaluate rapid, cost-effective surrogate endpoints to predict clinical efficacy. e. Develop strategies to detect, prevent, or overcome drug resistance. f. Develop novel treatment strategies such as extra corporeal treatment. g. Develop new assays based on molecular targets, especially those that may be amplified or altered in cancer cells. For example, develop assays for agents that interact with oncogenes, suppressor genes, signal transduction pathways, transcription factors, promoters. Assays based on molecular targets that are adapted for high volume screening of chemical libraries are especially encouraged as well as in vivo models, which can be used for "proof of concept" (i.e., validating the selectivity of the agent for the target). h. Develop cost-effective and useful techniques to improve in vitro cell culture methodology, such as the development of automated systems, serum-free media, or carbon dioxide-free buffering systems to stabilize cell culture performance. i. Identify and employ novel targets for antitumor drug discovery utilizing non-mammalian genetically defined organisms, such as fruit flies, worms, zebrafish and yeast. j. Develop array technologies for assays to evaluate activity. 3. Pharmaceutical Development a. Develop new methods to improve drug solubility for administration of promising antitumor compounds. b. Develop bioavailable alternatives to the intravenous delivery of cytotoxic chemotherapy. c. Develop improved methods to reduce thrombophlebitis and other related side effects observed following intravenous injection of some anticancer drugs. d. Develop new and innovative techniques for sterilization of parenteral dosage forms. e. Develop in vitro and in vivo models to predict human oral bioavailability of anticancer drugs. f. Develop practical delivery systems to deliver anticancer drugs to specific target sites. 4. Toxicology and Pharmacology a. Develop biochemical response profiles of specific target organs (e.g., bone marrow, gastrointestinal tract, liver, kidney, heart, lung) to permit rapid identification of toxic effects resulting from anticancer drug administration. b. Develop in vitro and/or in vivo tests for estimation and prediction of gastrointestinal toxicity, neurotoxicity (central and peripheral), cardiotoxicity, hepatotoxicity, nephrotoxicity and pulmonary toxicity. c. Correlate in vivo and in vitro models for organ toxicity as described above in 4b. Validate for various anticancer drugs. d. Develop drug metabolism (Phase I and Phase II) profiles for anticancer agents in human, mouse, rat and dog liver S-9, microsomes and slices. e. Develop systems to identify toxic effects of drugs by characterizing reactions with biomolecules or receptors. f. Develop in vitro tests to detect, qualify and quantify toxic effects of antineoplastic drugs. Develop techniques for determining individual variations in drug responses due to genetic polymorphisms or other factors. g. Develop a human somatic cell mutagenesis system. h. Develop personal computer programs for pharmacokinetics models capable of predicting drug behavior in humans from preclinical pharmacokinetics data in mice, rats, dogs, and non-human primates. i. Investigate and develop techniques for relating specific enzyme activities (both catabolic and anabolic) to body sizes of different species. j. Investigate techniques that would allow parameters, e.g., Km and Vmax for enzymes, to be scaled from preclinical to clinical models. k. Develop analytical strategies applicable to the quantitation of potent anticancer drugs in biological fluids at the pg/ml level, e.g., Halichondrin B and Bryostatin. l. Develop non-invasive techniques to determine drug distribution in various animal models. m. Develop gene array technology to determine normal (untreated) and toxicity (cancer drug treated) profiles utilizing samples from various cells and animal tissues. n. Evaluate interspecies transporter distribution and its impact on pharmacokinetic parameters, e.g., the impact of pharmacogentic variation in biodistribution. o. Determine optimal pharmacokinetic sampling schedules for use in dose titration/pharmacodynamic assessment by integrating information such as pre-clinical pharmacokinetic data, physico-chemical drug properties and mechanism of action. p. Determine which mouse/rat strains provide the most relevant data predict clinical situations (e.g., according to class of compound or mechanism of action). q. Develop an in vitro/in situ system for high throughput drug screens for oral bioavailability. r. Development and delivery of organ specific chemo-protective agents. 5. Animal Production and Genetics a. Investigate alternatives to expensive barrier systems for exclusion of pathogens from rodent colonies, e.g., by use of micro-isolator cages, and evaluate their performance. b. Develop and evaluate specialized shipping containers for pathogen-free animals. 6. Natural Product Discoveries. For the purposes of topics a, b, c, and e, examples of natural products in development are: Bryostatin, dolastatin 10, and halichondrin B. Note that execution of projects in most of these topic areas will require collaboration with countries where the source organism was originally collected. a. Investigate new biological methods, such as tissue culture, genetic engineering, aquaculture, hydroponics, etc., for the production of natural product potential anticancer or anti-HIV agents. b. Develop new systems of large-scale production using biotransformation, tissue or cell culture, biotechnology, modification of the chemical ecology of producing organisms, etc., in order to produce the large quantities of anticancer or anti-HIV drugs needed for preclinical or clinical development. c. Investigate newer methods of isolation and purification, such as super-critical fluid extraction and chromatography, centrifugal countercurrent chromatography or affinity-based separations, in the isolation and purification of natural products with anticancer or anti-HIV activity. d. Develop methods for the isolation, purification, identification, cultivation, and extraction of microorganisms from unusual marine or terrestrial habitats for antitumor and anti-HIV screening. Examples are gliding bacteria, psychrophilic, barophilic, endophytic, thermophilic, and tropical canopy organisms. e. Develop simple immunoassays that can be used to monitor the levels of natural products of interest in simple extracts of the relevant raw material. These assays should be capable of being developed for use "in the field" and also in developing countries. f. Develop techniques for the study of non-culturable organisms in order to identify antitumor agents. 7. Data Management Systems a. Develop data support systems for chemical library programs. b. Develop bioinformatic tools to accelerate the identification, functional understanding and validation of drug targets. c. Develop "data mining" strategies such as neural networks. C. Cancer and Nutrition. Research to improve the methodology of nutritional assessment in a cancer population. Innovative approaches to evaluate the contribution of nutritional status to response to cancer treatment. 1. Research to improve the methodology of nutritional assessment in a cancer population. 2. Develop means to evaluate the contribution of nutritional status to response to cancer treatment. D. Clinical Treatment Research. Clinical research studies designed to improve cancer treatment. Emphasis is on clinical trials for the evaluation of new therapeutic agents, development of assay systems to measure patient response to chemotherapy, development of prognostic assays, and development of methods of analysis and management of clinical trials data. 1. Evaluation of New Cancer Therapies a. Conduct clinical trials for the evaluation of new therapeutic agents or modalities of treatment employing drugs, biologics or surgery. b. Clinical trials using "unconventional therapies", including, but not limited to, behavioral and psychological approaches, dietary, herbal, pharmacologic and biologic treatments, and immuno-augmentative therapies. c. Development and evaluation of new clinical approaches using gene transfer or gene therapy technologies. d. Development and evaluation of new clinical approaches using tumor associated antigens or vaccines in order to enhance immunogenicity. e. Develop and characterize novel chemical compounds that may be useful anticancer agents, either alone or in combination with other modalities such as radiotherapy. f. Develop techniques to lessen the toxicity of existing anticancer treatments. g. Develop new techniques for the delivery of anticancer agents that will maximize therapeutic effects and minimize toxicity. h. Develop new surgical techniques or tools or improve existing techniques that are/may be utilized in cancer treatment. i. Characterize and produce clinical grade monoclonal antibodies to detect and treat malignancies. 2. Development of Prognostic Assays to Monitor Patient Response to Therapies a. Develop assay systems to measure the response of human tumors to chemotherapy or biologics. b. Characterize drug resistance mechanisms and design methods to overcome clinical drug resistance. c. Develop assays for prognostic factors to identify patient subsets who may benefit from specific cancer treatment therapies. d. Development of assays to assess effects of agents on specific molecular targets in clinical studies. e. Develop new techniques for relating past preclinical information to past clinical results for prediction of future useful clinical agents from future preclinical data (both in vitro and in vivo). 3. Clinical Trials Informatics a. Develop new tools and methodologies for the analysis of clinical trials results. b. Develop new informatics tools to facilitate clinical trials data entry from the bedside and coordination of data entry and transmission throughout the institution and to other collaborating institutions or organizations. c. Development of novel web-based approaches to clinical trials informatics for transmission of data to NCI or other organizations. Topics include point of treatment data capture and reporting, electronic protocols, OLAP (On-line Analytical Processing), support for the Common Toxicity Criteria, and drug accountability support. d. Develop new interchange standards, based on technologies such as XML, for sharing data among heterogeneous systems. Specific applications areas include, Adverse Even Reporting, Case Report Forms. e. Develop new tools for support of Common Data Elements. f. Develop new approachs for interface with electronic medical records, with intent to streamline data reporting, registration, and toxicity reporting of Clinical Trial information. E. Diagnostic and Medical Imaging Systems. The development of imaging technology and in vivo imaging methods as required for research or clinical investigations using either pre-clinical models or human subjects. The research scope includes: (1) diagnostic imaging with ionizing or non-ionizing radiation and/or any other types of in vivo imaging technology or imaging methods; and (2) research related to the biological and health effects of diagnostic and/or combined diagnostic/therapeutic procedures. Suggested areas may include: 1. Development of in-vivo instrumentation and contrast enhancement methods for non-invasive and minimally invasive imaging/spectroscopy methods, including imaging investigations at different resolution, spectral and temporal scales as required at both the anatomical and cellular/molecular level. Methods include: (1) molecular imaging, (2) functional imaging, (3) anatomical imaging and (4) combined modality imaging. Non-invasive imaging methods include transrectal, transvaginal, and endoscopic probes. Minimally invasive methods include the use of interventional techniques such as image-guided surgery or image-guided biopsy or therapy. Physical probes or implanted devices that allow imaging and/or spectroscopy measurement in vivo are also included. Comparisons with invasive procedures are appropriate for validation of imaging methods. 2. Developments of imaging system hardware and software components and other equipment that augment in vivo imaging/spectroscopy modalities, (i.e., X-ray, ultrasound, magnetic resonance, nuclear medicine, and optical or other imaging/spectroscopy technologies). 3. Development and evaluation of contrast methods or contrast enhancement agents, both intrinsic and extrinsic. These may be needed for all of the above in vivo imaging/spectroscopy modalities. 4. Development and evaluation of computer hardware and software for medical imaging, such as computer workstations, image processing methods, and informatics methods for image interpretation, image perception, and related outcome analysis. 5. Development and evaluation of image guided tools and methods for biopsy, surgery, therapy ( including non-sealed sources), imaging means for monitoring and verification of treatment fields before and/or during all modes of therapy, including therapy response. 6. Research in radiation biology and radiation physics relevant to in-vivo imaging/spectroscopy methods. F. Radiation Research. The Radiation Research Program (RRP) supports basic, developmental, and applied (clinical) research related to cancer treatment utilizing ionizing and non-ionizing radiations. Therapeutic modalities include photon therapy, particle therapy, photodynamic therapy (PDT), hyperthermia, radioimmunotherapy (RIT), and boron neutron capture therapy (BNCT). Radiation research encompasses a range of scientific disciplines including basic biology, chemistry, physics, and clinical radiation oncology. Topics of interest include, but are not limited to the following areas: 1. Develop devices for delivering radiation therapy or related therapies, including software related to treatment delivery, devices for patient positioning, and quality assurance for the following devices: (1) ionizing radiation, particularly for 3-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT); (2) ensuring reproducible patient setup and immobilization, particularly for 3DCRT and IMRT; (3) PDT; (4) hyperthermia; (e) RIT; and (5) epithermal neutron sources for BNCT. 2. Develop devices for dosimetry: (1) ionizing radiation; (2) PDT, particularly those capable of measuring light doses at depth in tissues; (3) thermometry for hyperthermia, particularly non-invasive thermometry; (4) RIT; and (5) BNCT. Devices may include chemical, solid state, film, biological, or ionization systems to detect or read out exposures. Accuracy, precision, and linear response is essential over the range of doses and temperatures employed in the research laboratory and/or in the clinic, depending on their intended use. Devices for thermometry during hyperthermia treatment must give accurate readings with the heating device(s) with which they are to be used. 3. Develop drugs to make radiation therapy or related therapies more effective: (1) chemical modifiers of radiation response, particularly small molecules and gene-based therapies; (2) photosensitizers for PDT; (3) sensitizers for use with hyperthermia; and (4) boron-containing compounds for BNCT. 4. Develop drugs to prevent, reduce, or reverse normal tissue response, especially the late effects that develop months or years after therapy. Compounds that are based on a rationale for achieving a therapeutic gain (an improved differential response between tumor and normal tissue) are of greatest interest. Enhancement of response must be achieved at radiation doses and treatment schedules employed clinically. 5. Develop predictive assays and monitors of response to therapy employing radiation, PDT, hyperthermia, BNCT, or RIT. Tools to identify patients that would benefit from specific therapeutic approaches are needed. G. Biological Response Modifiers (BRM). Research on agents or approaches that alter the relationship between tumor and host by modifying the host's biological response to tumor cells with resultant therapeutic benefits. Both preclinical and clinical investigations are conducted on the utility of a wide variety of natural and synthetic agents and on biological manipulations of immunological and non-immunological host mediated, tumor-growth controlling mechanisms in cancer therapy. In addition, development of new approaches to modify host responses to the human immunodeficiency virus (HIV) is included in the scope of this announcement. Studies are encouraged which utilize in vitro assays and/or animal model systems to investigate mechanisms of BRMs. Examples of innovative research that would be responsive to this solicitation include: 1. Application of observations describing shared receptors and mediators between the neuroendocrine and immune systems in studying immunobiology and immunotherapy of cancer or AIDS. 2. Evaluation of molecular genetic approaches to discovery of new therapeutic agents, delivery of BRMs, or development of gene therapy. 3. Studies of new agents active in inhibiting the development and/or reversing, multidrug resistance at the genetic and immunological level. 4. Development of improved techniques to synthesize, screen and develop new oligonucleotides for anti-oncogene or anti-viral effects. 5. Improvement in cell-culturing techniques, e.g., by developing automated cell culture systems, specialized media, or improved methods to induce activation, proliferation or differentiation. 6. Determination of new antitumor therapeutic approaches with maturation, differentiation or growth properties. 7. Development of new procedures or reagents for the modulation of the suppressor arm of the immune system in experimental models, directed towards successful immunotherapy. 8. Improvement of tumor-associated antigens or vaccines in an attempt to enhance immunogenicity. 9. Development of novel in vitro assays for the primary screening of BRMs. Other Research Topic(s) Within Mission of Institute Ms. Kay Etzler National Cancer Institute Office of Technology and Industrial Relations 31 Center Drive, MSC 2590 Bethesda, MD 20892-7395 (301) 496-1550; Fax: (301) 496-7807 Email: etzlerk@mail.nih.gov Website: http://www.cancer.gov/small business Division of Cancer Biology http://www.nci.nih.gov/dcb/dcbhom.htm Dr. Grace S. Ault National Cancer Institute Tumor Biology Branch, DCB 6130 Executive Boulevard, Room 530 Bethesda, MD 20892 301-435-1878; Fax: (301) 480-0864 Email: ga5k@nih.gov Division of Cancer Control and Population Sciences http://dccps.nci.nih.gov/mtgp Cancer Epidemiology and Genetics Mr. Jay Choudhry National Cancer Institute 6130 Executive Boulevard, Room 240 Bethesda, MD 20892 (301) 435-6613; Fax: (301) 402-4279 Email: choudhrj@mail.nih.gov Multimedia Technology and Health Communication in Cancer Control Ms. Connie Dresser National Cancer Institute 6130 Executive Boulevard, Room 232 Bethesda, MD 20892-7332 (301) 496-8520; Fax: (301) 480-6637 Email: cd34b@nih.gov Division of Cancer Treatment and Diagnosis Technology Development Branch Dr. Jennifer Couch National Cancer Institute 6130 Executive Boulevard, Room 6035A Bethesda, MD 20892 (301) 402-4185; Fax: (301) 402-7819 E-mail: jc332a@nih.gov Biochemistry and Pharmacology Dr. George S. Johnson National Cancer Institute 6130 Executive Boulevard, Room 841 Bethesda, MD 20892-7456 (301) 496-8783; Fax: (301) 402-5200 E-mail: gj16m@nih.gov Cancer Therapy Evaluations Program Dr. Diane Bronzert National Cancer Institute 6130 Executive Boulevard, Room 734 Bethesda, MD 20892-7432 (301) 496-8866; Fax: (301) 480-4663 Email: db85g@nih.gov Biomedical Imaging Program Dr. Manuel J. Torres-Anjel National Cancer Institute 6130 Executive Boulevard, Room EPN 6-046 Bethesda, MD 20892-7337 (301) 496-0735; Fax: (301) 480-3507 Email: mt71d@nih.gov Radiation Research Program Helen B. Stone, Ph.D. National Cancer Institute 6130 Executive Blvd.,Room EPN 6010 Bethesda, MD 20892-7440 (301) 496-9360; Fax: (301) 480-5785 Email: stoneh@exchange.nih.gov Biological Response Modifiers Dr. Craig Reynolds Biological Resources Branch National Cancer Institute-FCRDC PO Box B Building 1052 Room 253 Frederick MD 21702-1201 (301) 846-5693; Fax: (301) 846-5429 Email: cr45u@nih.gov Division of Cancer Prevention Dr. Barry Portnoy National Cancer Institute 31 Center Drive, Room 10A49 Bethesda, MD 20892-2580 (301) 496-9569; Fax: (301) 496-9931 Email: bp22z@nih.gov For administrative and business management questions, contact: Ms. Kathleen J. Shino Grants Management Specialist National Cancer Institute 1103 West 7th Street, Suite 300 Frederick, MD 21701-4106 (301) 846-1016; Fax: (301) 846-1198 Email: ks48e@nih.gov For additional NCI-related SBIR Information, contact: http://www.cancer.gov/smallbusiness NOTE: The Solicitations listed on this site are partial copies from the various SBIR agency solicitations and are not necessarily the latest and most up-to-date. For this reason, you should always use the suggested links on our reference pages. These will take you directly to the appropriate agency information where you can read the official version of the solicitation you are interested in. The official link for this page is: http://grants.nih.gov/grants/funding/sbir.htm. Solicitation closing dates are: April 1, August 1, and December 1, 2001.