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Rapid Protease Profiling with a Multiplex Electronic Method for Detection of Metastatic Triple-Negative Breast Cancer

Award Number: R01CA217657
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2017
PERIOD OF PERFORMANCE END DATE: 07/31/2022

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Rapid Protease Profiling with a Multiplex Electronic Method for Detection of Metastatic Triple-Negative Breast Cancer - Early diagnosis via cost-effective screening of high risk subpopulation followed by effective treatments is the key for saving many lives of cancer patients. Proteases overexpressed in cancer cells and secreted into circulation have been used as drug targets for the development of protease inhibitors as well as biomarkers for diagnosis and therapeutic monitoring. In this project, a multi-discipline team intends to develop a nanoelectronic chip for rapid profiling activity of six proteases that are overexpressed in metastatic triple-negative breast cancer (TNBC) patients and use this information to identify signatures in breast cancer progression and therapeutic responsiveness. The team includes (1) Dr. Jun Li (PI, nanotechnology and biosensor, Kansas State University); (2) Dr. Duy H. Hua (synthetic medicinal chemistry, Kansas State University); (3) Dr. Meyya Meyyappan (nanotechnology and nanodevices, NASA Ames Research Center); and (4) Dr. Priyanka Sharma (cancer clinical research, the University of Kansas Medical Center). This project focuses on developing the PI’s previously demonstrated electronic device based on carbon nanofiber nanoelectrode arrays for simultaneous detection of the activity of six overexpressed proteases in TNBC, including cathepsin B, MMP-2, MMP-9, ADAM-10, ADAM- 17 and uPA. Hexapeptide substrates highly specific to the aforementioned proteases are covalently attached to the tips of embedded carbon nanofibers in a multiplexed electronic chip. The distal end of the hexapeptides is attached with an electrochemical reporter. Introducing the TNBC patient samples containing these proteases results in cleavage of corresponding hexapeptides, thereby releasing the electrochemical reporter and leading to an exponential decrease of the electrochemical signal. The protease activity can be derived from the decay time constant of the kinetic curves. This extremely sensitive biosensor technology will be fabricated into independently addressed 3x3 arrays and packaged in disposable fluidic cartridges. Using 18 hexapeptide substrates (3 for each protease) attached to different nanoelectrode arrays in two 3x3 electronic chips, reliable proteolytic activity profile of the aforementioned six proteases in TNBC can be quickly measured, which cannot be done with current technologies. This technique should greatly accelerate the speed of protease profiling in complex samples and facilitate detection of invasive TNBC from other breast cancers in its early stage. The change of the protease activity profile will be monitored and correlate it with the longitudinal cancer treatment responses.


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: 2023 ( Subtotal = $0 )
2023	2020	KANSAS STATE UNIVERSITY	1601 VATTIER STREET	MANHATTAN	KS	66506	RILEY	USA	Cancer Detection and Diagnosis Research	001	4	5/12/2023	NON-COMPETING CONTINUATION	$0
2023	2020	KANSAS STATE UNIVERSITY	1601 VATTIER STREET	MANHATTAN	KS	66506	RILEY	USA	Cancer Detection and Diagnosis Research	000	4	12/2/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $278,547 )
2020	2020	KANSAS STATE UNIVERSITY	2 FAIRCHILD HALL	MANHATTAN	KS	66506	RILEY	USA	Cancer Detection and Diagnosis Research	000	4	7/24/2020	NON-COMPETING CONTINUATION	$278,547
														Subtotal = $278,547

Issue Date FY: 2019 ( Subtotal = $303,191 )
2019	2019	KANSAS STATE UNIVERSITY	2 FAIRCHILD HALL	MANHATTAN	KS	66506	RILEY	USA	Cancer Detection and Diagnosis Research	000	3	7/3/2019	NON-COMPETING CONTINUATION	$303,191
														Subtotal = $303,191

Issue Date FY: 2018 ( Subtotal = $380,137 )
2018	2018	KANSAS STATE UNIVERSITY	2 FAIRCHILD HALL	MANHATTAN	KS	66506	RILEY	USA	Cancer Detection and Diagnosis Research	000	2	6/12/2018	NON-COMPETING CONTINUATION	$380,137
														Subtotal = $380,137

Issue Date FY: 2017 ( Subtotal = $400,057 )
2017	2017	KANSAS STATE UNIVERSITY	2 FAIRCHILD HALL	MANHATTAN	KS	66506	RILEY	USA	Cancer Detection and Diagnosis Research	000	1	8/1/2017	NEW	$400,057
														Subtotal = $400,057

Grand Total All Awards = $1,361,932

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Rapid Protease Profiling with a Multiplex Electronic Method for Detection of Metastatic Triple-Negative Breast Cancer

Award Number: R01CA217657

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2017

PERIOD OF PERFORMANCE END DATE: 07/31/2022

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