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DESIGN OF THERAPEUTIC STRATEGIES SPECIFIC FOR BREAST CANCER INITIATING CELLS

Award Number: R01CA133797
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/10/2008
PERIOD OF PERFORMANCE END DATE: 01/31/2013

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DESIGN OF THERAPEUTIC STRATEGIES SPECIFIC FOR BREAST CANCER INITIATING CELLS - DESCRIPTION (provided by applicant): Breast cancer is the most common malignant tumor of females in the western hemisphere, with 178,500 new cases expected for 2007 in the U.S. alone. A growing body of evidence suggests that breast cancer growth is sustained by rare self-renewing cells, named breast cancer stem cells or breast cancer-initiating cells (BCIC), which are biologically distinct from their more numerous differentiated progeny. Although the design of therapies that eradicate BCIC has the potential to revolutionize the treatment of breast cancer, the identification of molecular therapeutic targets in BCIC isolated from human primary breast cancer specimens is an extremely difficult task. Several groups, including ours, have recently identified a sub-population of cancer-initiating cells (CIC) in several cell lines, including human breast carcinoma cell lines, opening the possibility to study BCIC in a readily available and abundant biological material. Specifically, we have found that mammary carcinoma, glioblastoma, melanoma cell lines and their single-cell clones contain cells capable of forming spheroids upon in vitro growth under stem cell-like conditions. Spheroid-forming cells displayed a gene expression profile consistent with CIC, increased tumorigenicity, and an altered pattern of chemosensitivity. We have also isolated by limiting dilution from the human breast carcinoma cell line MCF-7 the highly tumorigenic MCF-7/1-eGFP clone that expresses BCIC-associated surface markers. Based on these findings, we propose the long-term goal to design therapeutic strategies that preferentially target BCIC. The specific hypothesis is that we can design specific anti-BCIC therapeutic strategies directed against the products of genes over-expressed in human BCIC- enriched cell lines. First, we will develop BCIC models from human breast cancer cell lines. Then, we will identify genes over-expressed in BCIC by gene expression profiling. Finally, we will validate genes over-expressed in BCIC as breast cancer therapeutic targets. PUBLIC HEALTH REVELANCE: Breast cancer is the most common malignant tumor of females in the western hemisphere, with 178,500 new cases expected for 2007 in the U.S. alone. A growing body of evidence suggests that breast cancer growth is sustained by rare self-renewing cells, named breast cancer stem cells or breast cancer-initiating cells (BCIC), which are biologically distinct from their more numerous differentiated progeny. We propose to identify genes preferentially expressed in BCIC and to validate them as potential specific targets for breast cancer therapy.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2012 ( Subtotal = $253,788 )
2012	2012	ROSEMAN UNIVERSITY OF HEALTH SCIENCES	11 Sunset Way	HENDERSON	NV	89014	CLARK	USA	Cancer Treatment Research	000	6	9/20/2012	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$253,788
														Subtotal = $253,788

Issue Date FY: 2011 ( Subtotal = $326,066 )
2011	2011	NEVADA CANCER INSTITUTE	1000 WEST CHARLESTON BOULEVARD	LAS VEGAS	NV	89135	CLARK	USA	Cancer Treatment Research	001	5	5/13/2011	NON-COMPETING CONTINUATION	$23,531
2011	2011	NEVADA CANCER INSTITUTE	1000 WEST CHARLESTON BOULEVARD	LAS VEGAS	NV	89135	CLARK	USA	Cancer Treatment Research	000	5	1/12/2011	NON-COMPETING CONTINUATION	$302,535
														Subtotal = $326,066

Issue Date FY: 2010 ( Subtotal = $363,602 )
2010	2010	NEVADA CANCER INSTITUTE	1000 WEST CHARLESTON BOULEVARD	LAS VEGAS	NV	89135	CLARK	USA	Cancer Treatment Research	003	4	2/1/2010	NON-COMPETING CONTINUATION	$336,150
2010	2009	NEVADA CANCER INSTITUTE	1000 WEST CHARLESTON BOULEVARD	LAS VEGAS	NV	89135	CLARK	USA	Cancer Treatment Research	001	3	1/19/2010	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$211,324
2010	2009	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BOULEVARD	MOBILE	AL	36688	MOBILE	USA	Cancer Treatment Research	002	2	1/19/2010	NON-COMPETING CONTINUATION	$27,452
2010	2009	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BOULEVARD	MOBILE	AL	36688	MOBILE	USA	Cancer Treatment Research	000	2	1/19/2010	NON-COMPETING CONTINUATION	-$211,324
														Subtotal = $363,602

Issue Date FY: 2009 ( Subtotal = $274,523 )
2009	2009	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BOULEVARD	MOBILE	AL	36688	MOBILE	USA	Cancer Treatment Research	001	2	3/19/2009	NON-COMPETING CONTINUATION	$27,452
2009	2009	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BOULEVARD	MOBILE	AL	36688	MOBILE	USA	Cancer Treatment Research	000	2	1/15/2009	NON-COMPETING CONTINUATION	$247,071
														Subtotal = $274,523

Issue Date FY: 2008 ( Subtotal = $274,523 )
2008	2008	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BOULEVARD	MOBILE	AL	36688	MOBILE	USA	Cancer Treatment Research	000	1	4/10/2008	NEW	$274,523
														Subtotal = $274,523

Grand Total All Awards = $1,492,502

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DESIGN OF THERAPEUTIC STRATEGIES SPECIFIC FOR BREAST CANCER INITIATING CELLS

Award Number: R01CA133797

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/10/2008

PERIOD OF PERFORMANCE END DATE: 01/31/2013

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