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Necrosis-mediated circulating tumor cell dissemination

Award Number: F31CA260932
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 03/01/2022
PERIOD OF PERFORMANCE END DATE: 03/15/2023

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Necrosis-mediated circulating tumor cell dissemination - ABSTRACT Circulating tumor cells (CTCs) give rise to metastases, the major cause of cancer patient mortality. Despite its long-standing importance, what mediates CTC dissemination remains incompletely understood. One barrier has been the rarity of CTCs in patients and even more so in mouse models. Recently, I have developed an in vivo metastasis model for CTCs using rats. Compared with mice, I can robustly collect 10 to 20 times more blood using rats and obtain many more CTCs. Importantly, I observed that high CTC burden is associated with intratumoral necrosis, a form of inflammatory cell death. Furthermore, I have found temporal correlation between increase in intratumoral necrosis and CTC dissemination where there is a sudden 380-fold increase in CTC counts coinciding with increase in necrosis in the primary tumor. I hypothesize that necrosis in the primary tumor induces a high CTC dissemination state. I will test this hypothesis by 1) determining whether necrosis in the primary tumor is sufficient and necessary for a high CTC dissemination state 2) investigating whether CTC dissemination preferentially occurs in the necrotic regions of the primary tumor and 3) identifying necrotic tumor microenvironment markers associated with high CTC dissemination states. Uncovering the relationship between necrosis and CTC dissemination could enable selecting patients with necrotic tumors or surrogate serum markers of necrosis for more aggressive therapy to disrupt the metastatic process, thereby decreasing cancer patient mortality.


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: 2024 ( Subtotal = -$6 )
2024	2023	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Research Manpower	000	3	12/28/2023	NON-COMPETING CONTINUATION	-$6
														Subtotal = -$6

Issue Date FY: 2023 ( Subtotal = $2,958 )
2023	2023	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Research Manpower	002	3	4/17/2023	NON-COMPETING CONTINUATION	-$39,472
2023	2023	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Research Manpower	000	3	2/28/2023	NON-COMPETING CONTINUATION	$42,878
2023	2022	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Research Manpower	003	1	5/15/2023	NEW	-$448
2023	2022	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Research Manpower	001	1	3/29/2023	NEW	$0
														Subtotal = $2,958

Issue Date FY: 2022 ( Subtotal = $41,936 )
2022	2022	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Research Manpower	002	1	6/3/2022	NEW	-$38,619
2022	2022	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Research Manpower	001	1	2/11/2022	NEW	$0
2022	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Research Manpower	003	2	6/3/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$39,335
2022	2022	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Research Manpower	000	1	2/11/2022	NEW	$41,220
														Subtotal = $41,936

Grand Total All Awards = $44,888

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Necrosis-mediated circulating tumor cell dissemination

Award Number: F31CA260932

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 03/01/2022

PERIOD OF PERFORMANCE END DATE: 03/15/2023

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