Molecular Target Drug Discovery for Cancer

Program Description

To promote a more molecularly-oriented, knowledge-based approach to cancer drug discovery and development, a new Molecular Targets for Drug Discovery program was initiated in 2000. Based on increased knowledge of molecules and processes gone awry in cancer cells, it was felt that the time was ripe to undertake studies to rationally identify and validate potential targets and exploit them for cancer prevention and treatment. While empirical approaches have yielded dividends, the new paradigm required new thinking. To encourage new approaches, four initiatives were competed using different grant mechanisms: Exploratory Grants (R21), Cooperative Agreements (U01), Competitive Supplements, and Small Business Innovative Research/Small Business Technology Transfer Grants (SBIR/STTR, R43/,R41). The Exploratory Grant (R21) and the Competitive Supplement mechanisms were recompeted in 2001. Because of the enthusiastic response, the Exploratory Grant (R21) and Small Business Innovative Research/Small Business Technology Transfer Grant (SBIR/STTR) initiatives were reissued in November 2002. The Exploratory Grants have been well received, especially by new investigators anxious to get into the field of drug discovery, as a lack of preliminary data is not an impediment in pursuing bright ideas.

Targets Proposed for Investigation

Collectively, the applications proposed a variety of molecular targets to investigate and exploit for cancer drug discovery and development. The investigations covered a variety of molecular processes such as signal transduction, cell cycle control, apoptosis, angiogenesis and transcriptional and translational regulation. Both genetic changes and epigenetic modifications were targeted. The focus ranged from events on the cell surface to deep in the nucleus and events in between. Targets included receptor protein kinases, cyclins and cyclin kinases, apoptosis inhibiting proteins, telomerase, DNA methylases, transcriptional and translational factors, and other proteins with broader function, such as heat-shock proteins and integrins. Some proposals were also directed at viral and immune targets. Investigational approaches were dictated by the objectives, and ranged from biophysical measurements such as X-ray crystallography and NMR and genetic measurements such as mutational analysis and expression profiling to discovery tools such as high throughput screening of combinatorial libraries.

Statistics

Mechanism Type	RFA/PA	Number of Applications
		Received	Funded
_______________________________________________________________________________
Exploratory Grants	PA CA 03-020	122	16
SBIR/STTR	PA CA 03-021	28	0

Recent Issuances:

Molecular Target Drug Discovery for Cancer: Exploratory Grants, PA-03-020, NIH Guide, November 7, 2002
(Letter of Intent Receipt Date: None; Application Receipt Date: February 1, 2003)Closed: 2/01/03
Molecular Target Drug Discovery for Cancer: SBIR/STTR, PA-03-021, NIH Guide, November 7, 2002
(Letter of Intent Receipt Date: None; Application Receipt Date: April 1, 2003)Closed: 4/01/03

Previous Competitions:

Molecular Target Drug Discovery for Cancer: Competing Supplements,
PAR-01-046, NIH Guide, February 6, 2001
(Letter of Intent Receipt Date: May 17, 2001; Application Receipt Date: June 14, 2001)
Closed: 6/14/01
Molecular Target Drug Discovery for Cancer: Exploratory Grants, PAR-01-045, NIH Guide, February 2, 2001
(Letter of Intent Receipt Date: May 17, 2001,Applications Receipt Date: June 14, 2001)
Closed: 6/14/01

Request for Application:

Molecular Target Drug Discovery for Cancer, CA-00-002, NIH Guide, February 16 2000
(Letter of Intent Receipt Date: June 6, 2000; Application Receipt Date: July 18, 2000)
Closed: 7/18/00

In addition to this RFA, the NCI announced three related initiatives (Program Announcements):

MolecularTarget Drug Discovery for Cancer: Exploratory Grants, PAR-00-060, NIH Guide, February 16, 2000
(Letterof Intent Receipt Date: June 6, 2000; Application Receipt Date: July 18,2000)
Closed: 7/18/00
Molecular Target Drug Discovery For Cancer: Small Business Grants, PAR-00-061, NIH Guide, February 16, 2000
Letter of Intent Receipt Date: June 6, 2000; Application Receipt Date: July 18, 2000)
Closed: 7/18/00
Molecular Target Drug Discovery For Cancer: Competing Supplements, PAR-00-062, NIH Guide, February 16, 2000
(Letter of Intent Receipt Date: June 6, 2000, Application Receipt Date: July 18, 2000)
Closed: 7/18/00

MTDD AWARDS: