NIH GUIDE, Volume 26, Number 6, February 21, 1997


P.T. 34



  Nucleic Acids 



National Cancer Institute


Annual Receipt Dates:  April 1, August 1 and December 1 for STTR

                       April 15, August 15, and December 15 for SBIR




The purpose of this notice is to emphasize the importance of this

research topic, development of novel technologies to support cancer

research, to the Technology Development Branch of the Cancer

Diagnosis Program, Division of Cancer Treatment, Diagnosis and

Centers (DCTDC), National Cancer Institute (NCI), National Institutes

of Health (NIH).  This research topic is of special interest to the

NCI, NIH, and is identified in the OMNIBUS SOLICITATION OF THE


on pages 64-65.  This notice is intended to encourage projects that

propose development of technologies in two areas:  the generation of

representational full length cDNA libraries and the development of

high throughput technologies for analysis of the spectrum of

molecular alterations in primary tumor tissues.  Investigators may

propose projects to develop and/or to implement one of these

technologies.  Ultimately the technologies or resources developed

with the technologies must be commercially viable and preferably

useful within a clinical setting.


Through the Small Business Innovative Research (SBIR) and Small

Business Technology Transfer (STTR) mechanisms, small businesses can

receive funding for early phase development of innovative

technologies and proof of principle studies leading toward

commercialization of these technologies.


The solicitations are available electronically through the NIH,

Office of Extramural Research "Small Business Funding Opportunities"

home page located at In

addition, a limited number of hard copies of the solicitations have

been produced.  Subject to availability, they may be obtained from

the PHS STTR/SBIR Solicitation Office, phone (301) 206-9385; fax

(301) 206-9722; Email:




The rapid increase in our understanding of tumor biology coupled with

the technology and data emerging from the human genome project, offer

the opportunity for a change in the way cancer research is done.  It

is becoming clear that cancer is not a single disease but many, and

that cancers arise from the gradual accumulation of genetic changes

in single cells.  It is not clear which changes and how many changes

are required to cause a cancerous state.  Technologies that make

possible the evaluation of multiple alterations in tumor tissue at

the level of DNA, RNA or protein will facilitate the identification

of genes involved in cancer and will provide diagnostic and

prognostic information useful for cancer patient management.  This

notice is intended to encourage technology development projects in

the following two categories:  representational, full length cDNA

libraries and high throughput technologies for analysis of the

spectrum of molecular alterations in primary tumor tissues


Representational, Full-Length cDNA Libraries:


Current technology for generating cDNA libraries allows the

production of representative libraries of partial genes or production

of more limited libraries of full length clones, which are generally

enriched for shorter genes.  In addition, technology exists to create

normalized (reduced redundancy) cDNA libraries.  However, it is not

currently possible to efficiently generate representational libraries

of full length cDNAs.  In order to derive the maximum benefit from

existing libraries and to find expressed genes not present in

existing libraries, new technologies for generating full length

representational cDNA libraries are necessary.


Investigators may propose to develop the novel technologies for

generating these libraries or, if they have existing, proven

technologies for this purpose, they may propose to generate

appropriate libraries using their existing technology.  Approaches

for demonstrating that the clones in the libraries encode the entire

sequence of the mRNA from which they were derived and contain a

representative sample of the original mRNA population of the selected

tissue must be described.  Investigators may also propose to develop

technologies for generating libraries which are enriched for genes

differentially expressed from appropriate tissues. Appropriate

tissues are those which will provide information about gene

expression during cancer initiation and/or progression.  In all

cases, the end result must be a technique or a resource which can be

made into a commercially viable product.  For example, applicants

applying through the STTR mechanism may propose to move technology

previously developed at an academic institution to a small business

for the purpose of producing specific libraries.  Applicants applying

through the SBIR mechanism may propose, for example, to develop novel

technologies for the construction of the cDNA libraries and to

commercialize either the methodology or the resulting libraries.  The

most desirable technologies will be those which are adaptable to

high-throughput systems.


High-Throughput Analysis of Tissue Samples:


Previous studies designed to correlate molecular alterations in

tumors with clinical parameters have suggested the potential

importance of measuring these changes as a part of clinical

decision-making.  The sequencing of the human genome and ongoing

development of technologies to analyze genetic alterations on a

genome-wide scale may soon make it feasible to simultaneously

evaluate all or a subset of the nucleic acid alterations in tumor

tissue.  Similar technologies to detect patterns of protein

expression or to detect changes in proteins functioning in pathways

of cellular regulation are also needed.  The continuing development

of both nucleic acid and protein based technologies will facilitate

the discovery of new alterations in tumor cells and, ultimately, the

rapid collection of diagnostic and prognostic information that may be

useful in cancer patient management.


Investigators should propose development of nucleic acid or protein

based technologies and studies to assess their use in analysis of

primary tumor specimens.  They may propose to develop a

high-throughput technology to characterize cancers at the molecular

level, to modify existing technologies for use in a clinical setting,

or to commercialize technologies that currently exist only in a

laboratory setting.  For example, applicants applying through he SBIR

mechanism might develop a high-throughput technology then collaborate

with an academic institution to procure appropriate tissue samples

for validation of their technology on clinical specimens.  Applicants

applying through the STTR mechanism might propose to move

technologies developed in an academic setting for the high-throughput

screening of tissue samples into the development of commercial kits

or devices. Technologies may be designed to analyze a variety of

alterations including genome-wide cytogenetic changes; mutations in

constellations of genes known to be important in tumor initiation and

progression, including genes that are members of pathways of cellular

regulation; analysis of all possible mutations in a single gene;

changes in patterns of gene expression at the level of both RNA and

protein; or changes in protein function.  Development of sample

preparation technologies and/or informatics systems to support

collection and evaluation of research data may also be proposed.




Inquiries are encouraged.  The opportunity to clarify any issues or

questions from potential applicants is welcome.


Direct inquiries regarding programmatic issues to:


Jennifer Couch, Ph.D.

Division of Cancer Treatment, Diagnosis and Centers

National Cancer Institute

6130 Executive Boulevard, Room 513, MSC 7388

Bethesda, MD  20892-7388

Telephone:  (301) 496-1591

FAX:  (301) 402-1037



Direct inquiries regarding fiscal matters to:


Ms. Kathleen Shino

Grants Management Office

National Cancer Institute

6120 Executive Boulevard, Room 243

Bethesda, MD  20892-7150

Telephone:  (301) 496-7800, ext. 248

FAX:  (301) 496-8601




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