You are here

Division of Cancer Biology

Description:

The Division of Cancer Biology (DCB) plans and directs, coordinates, and evaluates a grant- and contract-supported program of extramural basic research on cancer cell biology and cancer immunology, and cancer etiology, including the effects of biological, chemical and physical agents, in the promotion of cancer; maintains surveillance over developments in its program and assesses the national need for research in cancer biology, immunology and etiology; evaluates mechanisms of biological, chemical and physical carcinogenesis and subsequent tumor growth and progression to metastasis; tests for carcinogenic potential of environmental agents; and serves as the focal point for the Federal Government on the synthesis of epidemiological and experimental data concerning biological agents relating to cancer. For additional information, please visit our home page at http://www.nci.nih.gov/dcb/dcbhom.htm.

A. Cancer Cell Biology. The Cancer Cell Biology Branch (CCBB) seeks to understand the biological basis of cancer at the cellular and molecular level. This research utilizes lower eukaryote and animal models, and animal and human tumor cells and tissues to analyze the mechanisms responsible for the growth and progression of cancer. Specific research and technologies supported by CCBB include but are not limited to the following:

1. Development of novel methods and tools to study key aspects of programmed cell death including its regulation and modulation.

2. Development of methods to identify and isolate tissue-specific stem cells.

3. Development of markers associated with specific cellular processes or differentiation.

4. Development of novel techniques, tools, and vectors to transfer functional genes, proteins, antibodies, etc. into intact cells or organisms.

5. New or improved technologies for the efficient microdissection of tumor tissue sections to isolate and preserve human cancer cells appropriate for research.

6. Generation of new inbred genetic animal models that transmit defective or altered cancer-related genes.

7. Development of novel technologies, methodologies, tools, or basic instrumentation to facilitate basic cancer research (research tools).

8. Development of methods and tools to study processes of protein trafficking, post-translational modification, and degradation.

9. Development of novel methods and tools for the analysis of intracellular organelles.

10. Development of novel methods and tools to determine intracellular gradient status.

11. Improved extraction methodologies and tools for tumor specimens for the subsequent analysis of DNA, RNA, and proteins.

12. Development of new or improved methods to isolate intact cellular regulatory complexes for functional studies.

13. Development of novel methods and tools to examine key cellular communication pathways.

14. Improved extraction methodologies and tools for tumor specimens for the subsequent analysis of DNA, RNA, and proteins.

15. Development of new or improved methods to isolate intact cellular regulatory complexes for functional studies.

16. Development of novel methods and tools to examine key cellular communication pathways.

B. Cancer Etiology. The Cancer Etiology Branch (CEB) supports research that seeks to determine the role of chemical, physical and biological agents as factors or cofactors in the etiology of human and animal cancer. The biological agents of primary interest are DNA viruses, RNA viruses, AIDS and AIDS-associated viruses, although the research may encompass all forms of life including bacteria and other microbial agents associated with cancer and use animal models of cancer and cancer vaccines. Chemical Carcinogenesis studies are concerned with cancers initiated or promoted by chemical or physical agents. A wide range of approaches are supported, including studies of the genetics of cell transformation, mutagenesis, tumor promotion and DNA damage, as well as studies of basic biochemistry and molecular biology of oncogenic and suspected oncogenic agents, viral oncogenes and associated tumor suppressor genes, pathogenesis and natural history studies, animal models, and preventive vaccine research. Mechanistic studies are encouraged in areas such as metabolism, toxicity and physiological distribution of carcinogens, genetics and regulation of enzymes, biochemical and molecular markers, and organ and cell culture systems and animal models. Also of interest are studies on cancer etiology by environmental chemicals, tobacco consumption and exposure, nutritional hazards, alcohol, asbestos, silica, and man-made fibers. CEB supports studies on endogenous exposure to steroid hormones and the generation of oxygen radicals during normal metabolism, studies on phytoestrogens and xenoestrogens and their impact on the metabolism of endogenous estrogens. In addition, CEB supports the development of analytical technologies to facilitate studies relating to carcinogenesis and mutagenesis. Specific research and technologies supported by CEB include but are not limited to the following:

1. Development of reagents, probes, and methodologies to evaluate the etiologic role of oncogenic viruses and other microbial agents (such as bacteria) in human cancer.

2. Development of novel in vitro culture techniques for oncogenic viruses or other microbial agents associated with or suspected of causing human cancer.

3. Development of sensitive, simplified diagnostic kits or reagents for the detection of oncogenic viruses or other microbial agents.

4. Development and characterization of animal models for studies of the mechanism of cancer induction by viruses or other microbial agents. The animals should faithfully mimic the human diseases associated with the virus or other microbial agent.

5. Development of methods (e.g., new-anti-microbial compounds, new vaccine approaches) to avert the induction of neoplasia in humans and animals by oncogenic viruses or bacteria.

6. Development of other novel technologies, methodologies or instrumentation to determine the role of biological agents, especially viruses, in the etiology of cancer.

7. Development and validation of methods for food treatment, preparation, or processing that will reduce or eliminate carcinogen/mutagen content.

8. Development of rapid analytical techniques for the qualitative and quantitative detection and screening of xenobiotics, chemical contaminants, and carcinogens/mutagens in human foods and biological and physiological specimens.

9. Development of in vitro and in vivo models for basic studies of carcinogenesis in specific organ systems, such as the pancreas, prostate, ovary, central nervous system, kidney, endometrium, stomach, and upper aerodigestive tract.

10. Development of methods for the production of carcinogens, anticarcinogens, metabolites, biomarkers of exposure, oxidative damage markers, and DNA adducts, both labeled and unlabeled, which are neither currently available commercially nor offered in the NCI Chemical Carcinogen Reference Standard Repository. The production of these compounds, in gram quantities, is desired for sale/distribution to the research community.

11. Development of methods for detection, separation, and quantitation of enantiomeric carcinogens, metabolites, adducts, and biomarkers of carcinogen exposure.

12. Development of monoclonal antibodies that are specific for different carcinogen-nucleoside adducts and demonstration of their usefulness in immunoassays. Of particular interest are antibodies to alpha-beta unsaturated carbonyl compounds (such as acrolein and crotonaldehyde) which can form exocyclic nucleoside adducts with DNA, and immunoassays for carcinogen/protein adducts as potential biomarkers of exposure.

13. Development of immunoassays using monoclonal antibodies that are specific for different polymorphs of Phase I and II carcinogen-metabolizing enzymes and repair enzymes. Included, but not limited to, are antibodies to the cytochrome P450 isozymes, glutathione S-transferases, and N-acetyl transferases.

14. Development of rapid, sensitive, and quantitative assays for the identification and measurement of androgens, estrogens, phytoestrogens, and xenoestrogens in complex biological matrices.

15. Development of rapid analytical techniques for the direct measurement of ligand-protein receptor interactions and determination of binding coefficients.

16. Development of analytical instrumentation for the detection and quantitation of extremely low levels of Tritium (3H) or 3H and Carbon-14 (14C) from biological samples. Of particular interest is the development of small-sized, accelerator-based mass spectrometry equipment capable of measuring down to, or below, contemporary background levels of 3H and 14C that would make this sensitive technique more widely available to research groups. The design and development of technologically improved and miniaturized individual components, including ion source, sample preparation (autosampling apparatus), accelerator, and mass spectrometric detectors, are also solicited.

17. Synthesis of selective suicide inhibitors of cytochrome P450 isoforms and selective arachidonic acid pathway inhibitors/ enhancers for basic biochemical studies and anticarcinogenic potential.

18. Development of invertebrate animal models (such as Drosophila, C. elegans, clam, and sea urchin) for the study of environmental chemicals and/or hormonal carcinogenesis.

19. Development of more efficient and reliable methods of preserving valuable animal model gene stocks by innovative in vitro techniques.

20. Development of a defined diet for support and maintenance of aquatic and marine fish models of cancer including but not limited to swordtail, zebrafish, medaka, mummichog, guppy, Fugu, and Damselfish.

21. Development of serum free tissue culture media for aquatic and marine fish models of cancer.

C. Cancer Immunology and Hematology. The Cancer Immunology and Hematology Branch (CIHB) supports a broad spectrum of basic research focused on the earliest stages of hematopoiesis and tracing the molecular events that lead to the development of all the functional elements of the immune system and, when errors occur, to the development of leukemias and lymphomas. Most research of interest falls into three major areas. The first is the immune response to tumors to include studies of all of the cells (T, B, NK, antigen-presenting, and other myeloid cells) and secreted molecules (antibodies and cytokines) of the immune system that can recognize and affect tumor growth. Emphasis is placed on the alteration in the mechanisms responsible for the failure of immune response to eradicate most tumors under normal conditions, and the development of strategies to circumvent these mechanisms. A second major area of interest examines the biology of hematopoietic malignancies to describe the molecular biology reasons underlying the cell's failure to respond to normal growth controls and to develop novel approaches to prevention or therapy. The third distinct area supported is the basic biology of bone-marrow transplantation, including studies of host cell engraftment, graft-versus-host disease, and the basis of the graft-versus-leukemia effect. Specific research and technologies supported by CIHB include but are not limited to the following:

1. Development of improved or novel monoclonal antibody technologies including improvements of methodologies for fusion, production of novel cells as fusion partners, selection and assay of antibody producing clones, and production of new and improved monoclonal antibodies.

2. Synthesis, structure and function of antibodies capable of reacting with tumor cells, agents that induce tumors and agents used in the treatment of tumors.

3. Development of in vivo animal models systems that can be used to study the immune response to tumors and the mechanisms of immunotherapy.

4. Synthesis, structure and function of soluble factors that participate in, activate and/or regulate hematopoietic cell growth and the immune response to tumors, including interferons, other lymphokines and cytokines (interleukins), hematopoietic growth factors, helper factors, suppressor factors and cytotoxic factors.

5. Application of biochemical, molecular biological and immunological techniques for identifying tumor antigens that are good targets for the development of vaccine-type strategies of cancer immunotherapy.

6. Development of techniques to enhance the immune response to tumors, including modification of tumor cells and/or antitumor lymphocytes to facilitate cancer vaccine strategies.

7. Development of improved methodology for manipulating bone marrow inoculum to decrease the incidence of graft-versus-host disease without increasing the risk of graft failure or leukemic relapse.

8. Development of improved methodology for increasing the number of peripheral blood stem cells available for harvest for use in transplantation, including improved methods of identifying and removing residual leukemic cells in the autologous transplant setting.

9. Development of methods to identify and define human minor histocompatability antigens.

10. Development of novel culture systems to improve the expansion of lymphocytes and dendritic cells.

11. Development of the combination of cell culture and other research tools to better expand human hematopoietic stem cells.

12. Development of improved techniques for computational simulation/modeling of biological processes involved in immunologic defenses against tumor cells such as signal transduction, cell cycle progression, and intracellular translocation.

13. Development of other novel technologies, methodologies or instrumentation to facilitate basic research in either tumor immunology or cancer hematology.

14. Development of molecular, cellular or biochemical techniques to isolate and/or characterize tumor stem cells from hematologic malignancies.

D. DNA and Chromosome Aberrations. The DNA and Chromosome Aberrations Branch (DCAB) seeks to study the genome at the DNA and chromosome level, including discovery of genes at sites of chromosome breaks, deletions, and translocations; DNA repair; structure and mechanisms of chromosome alterations; epigenetic changes; radiation- and chemical-induced changes in DNA replication and other alterations; and analytical technologies. Specific research and technologies supported by DCAB include but are not limited to the following:

1. Development of new, improved technologies for characterization of chromosomal aberrations in cancer.

2. Development of new, improved, or high throughput technologies for whole genome scanning for chromosome aberrations in cancer.

3. New or improved technologies to increase accuracy of karyotypic analyses of tumor specimens.

4. New or improved methods to mutate or replace genes at specific sites in intact cells.

5. Development of new, sensitive methods to assess the methylation status of genes.

6. Development and distribution of genomic resources suitable for genomic manipulation or cytogenetic studies.

7. Technologies for assaying for mammalian genes relevant to repair of damage induced by exposure of mammalian cells to ionizing and non-ionizing radiations, with special emphasis on human cells.

8. Methods/approaches to study the repair of DNA lesions induced by exposure of mammalian cells to ionizing radiations (both high- and low-LET).

9. Development and characterization of human cell lines with specific DNA-repair deficiencies.

10. Development of genetic constructs that utilize radiation-responsive regulatory genes to control the expression of targeted structural genes in mammalian cells.

11. Development of new methods/technologies to assay transcription factor binding sites across whole genomes.

12. Use of RNAi and siRNA in the development of novel methods and tools for the study of gene expression, gene silencing, gene regulation, and genome-wide screening in cells and tissues.

13. Development and integration of nanotechnology and microfluidics in the analysis of DNA and chromosomal aberrations and the identification, mapping, and cloning of cancer susceptibility and resistance genes.

14. Development of human tumor cDNA library banks to study gene expression in cancer.

15. Generation of new or improved animal models or non-mammalian models (e.g. flies, worms) as research tools to study human cancers.

E. Mouse Models of Human Cancers Consortium. The Mouse Models of Human Cancer Consortium is a program based in the Office of the Director, DCB. The Consortium has the important goal of providing mouse cancer model-related resources and infrastructure to the research community, in part through various outreach activities. The outreach requirement generates the need for innovative educational or informational materials that convey the content of Consortium meetings and symposia, or document hands-on workshops in which models or techniques that are pertinent to mouse modeling are demonstrated. The instructional materials may be CD-ROMs, videotapes, Web-based interactive programs, or other media.

F. Structural Biology and Molecular Applications. The Structural Biology and Molecular Applications Branch (SBMAB) focuses on structural and molecular studies to explore the processes of carcinogenesis and tumorigenesis. Areas of interest include structural biology, genomics, proteomics, molecular and cellular imaging, enzymology, bio-related and combinatorial chemistry, bioinformatics, systems biology and integrative biology as they apply to cancer biology. Interests also include modeling and theoretical approaches to cellular and molecular dimensions of cancer biology. Specific research and technologies supported by SBMAB include but are not limited to:

1. Development of new, improved, or high throughput technologies for whole genome scanning for gene identification.

2. Development of systems that will automate the technology of culturing or assaying single cells.

3. New or improved technologies for efficient microdissection of tumor tissue sections for the development of tissue arrays.

4. Improved extraction techniques for tumor specimens for subsequent DNA, RNA, and protein analyses.

5. Rapid methods to isolate intact complexes of regulatory proteins and to separate and identify the proteins for biophysical studies.

6. New or improved technologies for the preservation of small amounts of DNA/RNA/protein samples

7. Development of new techniques and vectors for transfer of genes, proteins, and antisense molecules into cells.

8. Generation of software and computer models for the prediction of macromolecular structure and function.

9. Development of bioinformatic tools for the study of cancer biology including facilitating genome data, gene ?mining,? cluster analysis, and data base management.

10. Development of novel gene technology (e.g., microarray, differential display technology) for measurement of differential gene expression levels and functional genomics studies.

11. Development of novel proteomic tools for the analysis of protein expression in cancer biology.

12. Computer-based methodologies to assist in the understanding of signal transduction and cancer biology.

13. Methodologies and techniques for the imaging of macromolecules in vitro and in vivo.

14. Development of other novel technologies, methodologies or instrumentation to facilitate basic research (research tools) in cancer biology.

15. Develop new approaches and technologies for the structural determination of large biomolecular complexes.

16. Development and integration of nanotechnology approaches and tools in basic cancer biology research.

17. Application and development of novel approaches for in vivo and in vitro modifications of protein expression in cells and tissues, e.g. RNAi, microRNA, other small molecules.

18. Mathematical and theoretical models for the understanding of cancer biology.

19. Development of new software and lab analysis tools that will improve the recording and collection of data and experimental protocols in order to facilitate cancer biology research.

20. Technology and software for elucidating molecular interactions and networks.

21. Develop new, improved or high-throughput technologies for analyzing epigenomic changes.

22. Improved software for the integration of heterogeneous data sources.

23. Development of new, improved or high-throughput technologies for understanding the cancer metabolome.

G. Tumor Biology and Metastasis. This branch supports research that seeks to understand the interactions of cancer cells with the tumor and/or host microenvironment in order to delineate the molecular mechanisms and signaling pathways of tumor angiogenesis and lymphangiogenesis, cell migration and invasion, tumor progression, and metastasis. This includes examination of cell-cell and cell-matrix interactions, and the roles played by cell growth factors and cytokines, adhesion molecules, cytoskeleton and the nuclear matrix, and matrix-degrading enzymes, as well as studies on the pathology and biology of solid tumors and tumor bearing animals, and the development of technology to facilitate these studies. Emerging areas of emphasis are the microenvironment created by inflammation and the inflammatory signaling molecules in tumor initiation and progression and the role of somatic stem cells in determining tumor progression and metastatic behavior. Stem cell motility, positional information cues from surrounding tissue and adhesion properties together with issues of epithelial-mesenchymal transitions related to cancer progression are supported. Emphasis is also placed on the role of the extracellular matrix and tissue microenvironment during development and tissue morphogenesis, and on the role of glycoproteins in tumor growth, invasion, and metastasis. The branch also focuses on the function of steroid hormones, their receptors and coregulators during tumor growth and progression. Models utilized in these studies may include animal models, tumor tissues/cells, their components, or their products. The development of organotypic models that closely mimic in vivo models is encouraged. Specific research and technologies supported by TBMB include but are not limited to:

1. New technical strategies to identify and assess the function of components of the extracellular matrix.

2. Development of new in vitro cancer models to study the pathology and biology of solid tumors and tumor bearing animals.

3. New in vivo models of angiogenesis, lymphangiogenesis, cancer progression and metastasis.

4. Development of technologies to identify novel factors that modulate angiogenesis and lymphangiogenesis.

5. Identification of genes and/or enzymes associated with glycosylation in tumor cells.

6. Identification of novel coregulators of nuclear steroid receptor superfamily.

7. Development of improved techniques for computational simulation/modeling of biological processes involved in malignant transformation, persistence, or invasion, such as signal transduction, cell cycle progression, and intracellular translocation.

8. Development of new assays or methods to evaluate tumor cell invasiveness.

9. Development of new assays or methods to study molecules and pathways involved in cell-to-cell signaling or communication.

10. Development of appropriate new animal, cellular or organotypic models to study tumor stroma interactions, 3-D models that closely mimic in-vivo conditions.

11. Study roles of cytokines/growth factors released by host cells during inflammation, invasion, tumor progression and metastasis.

US Flag An Official Website of the United States Government