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Objectives and Scope
The purpose of these RFAs is to encourage applications from individuals and groups interested in developing novel technologies suitable for the molecular analysis of cancers and their host environment in support of basic, clinical, and epidemiological research. Technologies to support research in the following areas are considered to be appropriate. Examples given below are not intended to be all-inclusive but are illustrative of the types of capabilities that are of interest.
New tools that allow development of more complete molecular profiles of normal, precancerous, and cancerous cells, as well as the process of carcinogenesis, are needed to support the basic discovery process. The same sort of technological approaches will also be needed to examine the tumor micro-environment, including stromal and vascular interaction. These tools will also allow more thorough examination of the variations that influence predisposition to cancer and individual variability in response to therapeutic and prevention agents. Of interest are technologies and data analysis tools for:
- In vitro scanning for and identification of the sites of chromosomal aberrations that reflect inherited aberrations or somatic alterations resulting from aging, oxidation, or exposure to radiation or carcinogens, including those that are suitable for scaling for use across whole genomes, detecting DNA adducts, or detecting rare variants in mixed populations
- In vitro scanning for and identification of sites of mutations and polymorphisms that reflect inherited aberrations or variations, or somatic alterations resulting from aging, oxidation, or exposure to radiation or carcinogens, including those that are suitable for scaling for screening whole genomes, detecting DNA adducts, or identifying infrequently represented mutations in mixed populations of DNA molecules
- Technologies for detection and characterization of nucleic acid sequences of novel exogenous infectious agents that may be present in human cancer
- Highly specific and sensitive detection of specific mutations
- Detecting mismatch and recombinational DNA repair related to cancer susceptibility and drug sensitivity
- In vitro multiplexed analysis of the expression of genes
- In vitro detection of expression of proteins and their modified forms, including technologies suitable for expansion to profiling of all proteins expressed in cells, detecting rare variants in mixed populations, and detecting protein adducts involved in chemical mutation
- Monitoring the function of proteins and genetic pathways, including measurement of ligand-protein complexes and technologies for monitoring protein function of all members of a class of proteins or a complete genetic pathway
- Delineating molecular expression, function, and analysis at the cellular level in the context of both the whole body and in situ , including molecular imaging technologies suitable at this scale, contrast agents, gene amplification techniques, and related data analysis tools
- Detection technologies and sensors, including signal to noise optimization and rare cell/molecule detection, of cancer and the structures and molecules important in its development and diagnosis
- Technologies to elucidate molecular modifications of macromolecules that may be indicative of and critical to the transformation process
- Delivery technologies and approaches to enable faster and more accurate delivery of molecular and cellular labels and drugs to and within cells for research and treatment, the overall goals being speed, accuracy, and biocompatibility
- Development of high-throughput, quantitative assays for epigenetic alterations, e.g., acetylation and methylation, in promoter region of genes and histone proteins isolated from biological fluids and tissues
For all technologies proposed, it will be important to substantiate the ultimate value of and role for the technology in deciphering the molecular anatomy of cancer cells or analyzing the molecular profile of the individual. It is also important for applicants to discuss the ultimate potential for the transfer of ensuing technology to other laboratories or the clinic and, for more mature technologies, plans to ensure dissemination of the technology. In the case of technologies intended for use on clinical specimens or in patients, applications from or collaborations with investigators involved in the clinical research of cancer are encouraged.