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Cellular level optical metabolic imaging to predict drug response in cancer

Award Number: R01CA185747
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/16/2014
PERIOD OF PERFORMANCE END DATE: 08/31/2021

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Cellular level optical metabolic imaging to predict drug response in cancer - DESCRIPTION (provided by applicant): Each year, 33-43% of breast cancers (>100,000 cases) exhibit de novo resistance to initial therapeutic treatment strategies. Unfortunately, current technologies that guide initial treatment choices for breast cancer patients are inaccurate for identifying de novo resistance. This underscores the critical clinical need for earl, accurate, and cost-effective methods of selecting the most effective initial treatment for breast cancer patients. Early identification of those tumors that will respond to therapy versus those that are resistant will (1) expedite clinical decisions regarding the course of treatment, (2) improve the clinical outcomes of breast cancer patients by identifying those patients who are in need of alternate therapies, and (3) spare pre-identified unresponsive patients from the toxicities associated with ineffective treatment. The central goal of this proposal is to develop an innovative platform based on optical metabolic imaging technologies to directly measure de novo resistance of primary tumors and predict therapy response. Optical metabolic imaging (OMI) includes a unique combination of variables, developed by our lab, to accurately measure early drug response with cellular resolution. OMI exploits the intrinsic fluorescence intensities and lifetimes of the metabolic co-enzymes reduced nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) to probe cellular metabolism. Our innovative combination endpoint, the "OMI index," and unique cellular-level analysis provide unprecedented sensitivity to identify heterogeneous cellular drug response, which is critical to ensure that no malignant cells escape treatment. We have shown that OMI can accurately measure therapeutic response in breast tumors in vivo at an earlier time-point than currently used clinical techniques. Further, we have developed novel methods to culture primary human breast tumors in a three-dimensional collagen matrix (organoids), and have applied OMI to accurately, rapidly, and reproducibly predict in vivo tumor responses to multiple treatment schemes in these organoids. The novel and powerful predictive value of organoid testing and imaging could be used to optimize clinical treatment strategies prior to treatment using ex vivo biopsy samples. Therefore, the significance of OMI of primary tumor organoids lies in its potential to measure the dynamic cellular response to multiple treatment strategies within individual patient tumors. This approach could predict an optimal, individualized treatment strategy within hours, before the patient is actually treated. Significance: OMI of organoids derived from primary human tumors could serve as an accurate predictive test of de novo drug resistance across multiple types of cancers, thus transforming patient care to identify optimal treatment strategies before treatment is initiated. This work also has the potential to significantly accelerate pre-clinical drug discovery by developing sensitive in vivo measures of treatment response, and a high-throughput platform to test tumor response to multiple treatment schemes while reducing animal burden and read-out time.


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: 2022 ( Subtotal = -$1,522 )
2022	2019	THE MORGRIDGE INSTITUTE FOR RESEARCH, INC.	330 N ORCHARD ST	MADISON	WI	53715	DANE	USA	Cancer Detection and Diagnosis Research	000	6	12/15/2021	NON-COMPETING CONTINUATION	-$1,522
														Subtotal = -$1,522

Issue Date FY: 2019 ( Subtotal = $305,296 )
2019	2019	VANDERBILT UNIVERSITY, THE	2301 VANDERBILT PL	NASHVILLE	TN	37235	DAVIDSON	USA	Cancer Detection and Diagnosis Research	002	6	8/13/2019	NON-COMPETING CONTINUATION	$305,296
2019	2015	VANDERBILT UNIVERSITY, THE	2301 VANDERBILT PL	NASHVILLE	TN	37235	DAVIDSON	USA	Cancer Detection and Diagnosis Research	001	3	4/17/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1,578
2019	2014	VANDERBILT UNIVERSITY, THE	2301 VANDERBILT PL	NASHVILLE	TN	37235	DAVIDSON	USA	Cancer Detection and Diagnosis Research	000	1	4/17/2019	NEW	-$1,578
														Subtotal = $305,296

Issue Date FY: 2018 ( Subtotal = $314,739 )
2018	2018	VANDERBILT UNIVERSITY, THE	2301 VANDERBILT PL	NASHVILLE	TN	37235	DAVIDSON	USA	Cancer Detection and Diagnosis Research	000	5	8/20/2018	NON-COMPETING CONTINUATION	$314,739
														Subtotal = $314,739

Issue Date FY: 2017 ( Subtotal = $314,739 )
2017	2017	VANDERBILT UNIVERSITY, THE	211 KIRKLAND HALL	NASHVILLE	TN	37240	DAVIDSON	USA	Cancer Detection and Diagnosis Research	002	4	8/21/2017	NON-COMPETING CONTINUATION	$314,739
2017	2015	VANDERBILT UNIVERSITY, THE	211 KIRKLAND HALL	NASHVILLE	TN	37240	DAVIDSON	USA	Cancer Detection and Diagnosis Research	001	3	12/21/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$65,928
2017	2014	VANDERBILT UNIVERSITY, THE	211 KIRKLAND HALL	NASHVILLE	TN	37240	DAVIDSON	USA	Cancer Detection and Diagnosis Research	000	1	12/21/2016	NEW	-$65,928
														Subtotal = $314,739

Issue Date FY: 2016 ( Subtotal = $0 )
2016	2015	THE MORGRIDGE INSTITUTE FOR RESEARCH INC	330 NORTH ORCHARD STREET	MADISON	WI	53715	DANE	USA	Cancer Detection and Diagnosis Research	000	3	9/8/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$315,367
2016	2015	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	001	2	9/8/2016	NON-COMPETING CONTINUATION	-$315,367
														Subtotal = $0

Issue Date FY: 2015 ( Subtotal = $315,367 )
2015	2015	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	000	2	9/4/2015	NON-COMPETING CONTINUATION	$315,367
														Subtotal = $315,367

Issue Date FY: 2014 ( Subtotal = $315,367 )
2014	2014	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	000	1	9/16/2014	NEW	$315,367
														Subtotal = $315,367

Grand Total All Awards = $1,563,986

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Cellular level optical metabolic imaging to predict drug response in cancer

Award Number: R01CA185747

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/16/2014

PERIOD OF PERFORMANCE END DATE: 08/31/2021

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