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Exosomal Contents Guided Amino Acids Treatment for Pancreatic Cancer

Award Number: R21CA270748
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/02/2022
PERIOD OF PERFORMANCE END DATE: 12/31/2024

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Exosomal Contents Guided Amino Acids Treatment for Pancreatic Cancer - PROJECT SUMMARY/ABSTRACT With a 5-year survival rate of less than 5%, Pancreatic adenocarcinoma (PDAC) is a lethal condition with poor outcomes and an increasing incidence. Surgical resection is the only treatment that offers a potential cure, but was limited to the early stage cases without distant metastasis. Currently, there are scarce effective treatments for advanced disease. Chemoradiation and systemic chemotherapy are the mainstay of treatment to slow disease progression at advanced stages. But these therapies cause various side effects, which is one major barrier to the efficacy of anti-tumor therapeutics. There are no known medications that can selectively protect normal tissues from these side effects, and thus an urgent need for novel treatment selectively targeting only tumor cells to improve patient outcomes. Exosomes secreted by tumor cells actively participate in tumor progression and metastasis and contain multiple biomolecules reflecting the status of their parental tumor cells. Investigation of the exosomal contents may lead to a therapeutic inspiration for cancer. We conducted comparative proteomics studies over the malignant and nonmalignant cells at both the cellular and exosomal level. Significant different proteome sets have been identified between the malignant and nonmalignant cells at all levels. Since amino acids are the formation unit of the protein primary sequence, we furthered the proteomics results by studying the distribution of the amino acids statistically between the malignant and nonmalignant cells at both cellular and exosomal level. We found a significant imbalanced amino acid distribution between the tumor cells and exosomes, which is not found between nonmalignant cells and exosomes. This indicates that tumor cells selectively flux certain amino acids out of cells through exosomes, which inspired us to use these amino acids as stressors to tumor cells. The cell viability of the tumor cells treated by these amino acids was significantly decreased, but not that of nonmalignant cells. This exosome-guided observation potentiates a new therapeutic intervention selectively targeting tumor cells. In order to develop the finding into a therapeutic choice for pancreatic cancer, we propose to preclinically validate the treatment in vivo and study the mechanism in vitro.


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: 2025 ( Subtotal = -$51,753 )
2025	2023	NORTH DAKOTA STATE UNIVERSITY	1301 12TH AVE N	FARGO	ND	58102	CASS	USA	Cancer Treatment Research	001	2	2/14/2025	NON-COMPETING CONTINUATION	-$1
2025	2023	UNIVERSITY OF DENVER	2199 S UNIVERSITY BLVD RM 222	DENVER	CO	80210	DENVER	USA	Cancer Treatment Research	002	3	2/14/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$51,753
2025	2023	UNIVERSITY OF DENVER	2199 S UNIVERSITY BLVD RM 222	DENVER	CO	80210	DENVER	USA	Cancer Treatment Research	003	3	4/15/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$51,753
2025	2022	NORTH DAKOTA STATE UNIVERSITY	1301 12TH AVE N	FARGO	ND	58102	CASS	USA	Cancer Treatment Research	000	1	2/14/2025	NEW	-$51,752
														Subtotal = -$51,753

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	NORTH DAKOTA STATE UNIVERSITY	1310 BOLLEY DR	FARGO	ND	58105	CASS	USA	Cancer Treatment Research	000	2	12/29/2023	NON-COMPETING CONTINUATION	-$199,294
2024	2023	COLORADO SEMINARY	2199 S UNIVERSITY BLVD	DENVER	CO	80210	DENVER	USA	Cancer Treatment Research	001	3	12/29/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$199,294
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $199,295 )
2023	2023	NORTH DAKOTA STATE UNIVERSITY	1310 BOLLEY DR	FARGO	ND	58105	CASS	USA	Cancer Treatment Research	000	2	1/31/2023	NON-COMPETING CONTINUATION	$199,295
														Subtotal = $199,295

Issue Date FY: 2022 ( Subtotal = $169,469 )
2022	2022	NORTH DAKOTA STATE UNIVERSITY	1919 UNIVERSITY DR N, STE 102	FARGO	ND	58102	CASS	USA	Cancer Treatment Research	000	1	2/2/2022	NEW	$169,469
														Subtotal = $169,469

Grand Total All Awards = $317,011

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Exosomal Contents Guided Amino Acids Treatment for Pancreatic Cancer

Award Number: R21CA270748

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/02/2022

PERIOD OF PERFORMANCE END DATE: 12/31/2024

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