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Platelet FcGammaRIIa and Risk of Venous Thromboembolism in Cancer

Award Number: R21CA267074
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2025

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Platelet FcGammaRIIa and Risk of Venous Thromboembolism in Cancer - Thrombosis is common and contributes significantly to morbidity and mortality in patients with cancer. At least 20% of patients with cancer develop venous thromboembolism (VTE) and another 5% will experience acute arterial thromboembolism (ATE) due to cancer and its treatment. Current guidelines recommend VTE thromboprophylaxis in high-risk outpatients. Thromboprophylaxis strategies are inadequate as 50% of high- risk patients on prophylaxis still develop a VTE, the rate of recurrent VTE is ~24% with a case fatality rate of 14.8%, and the incidence of major bleeding is ~13% with a case fatality rate of 8.9%. We and others have implicated platelets in both the pathogenesis of VTE as well as cancer growth and metastasis. To investigate a new biomarker of risk in patients with cancer, we propose a pilot study to determine whether quantification of platelet FcɣRIIa expression can discriminate risk of VTE and cancer progression. We chose platelet FcɣRIIa expression because we have found that quantifying platelet surface expression of FcγRIIa identifies patients at high and low risk of thrombotic arterial events. Thus, we hypothesize that elevated platelet expression of FcγRIIa will identify patients with cancer who are greater risk of VTE as well as cancer progression. The proposed studies leverage a clinical research program that was established in 2015 at the University of Vermont Cancer Center (Venous Thromboembolism Prevention in the Ambulatory Care Clinic [VTEPACC]) and will allow simultaneous access to research samples, thrombosis complications and cancer outcomes in order to achieve the following specific aims: 1) To determine whether platelet expression of FcγRIIa identifies cancer patients at high and low risk of VTE, and 2) To determine whether increased platelet expression of FcγRIIa is associated with a) advanced stage cancer at the time of enrollment and b) greater progression of cancer. Platelet reactivity is increased in patients with cancer and has been associated with VTE risk. Platelet expression of FcγRIIa can increase the risk of thrombosis by both increasing platelet reactivity and by promoting the procoagulant potential of platelets. In addition, platelets promote cancer by facilitating tumor vascularization, growth, and metastasis. FcγRIIa has been shown to be a key mediator of platelet secretion and cross-talk between platelets and tumor cells. Thus, we propose that increased platelet FcγRIIa expression will be linked to enhanced tumor growth and metastasis by facilitating cancer-tumor cell cross-talk and thereby the activation of platelets that leads to the release of platelet products. Identification of a biomarker capable of discriminating high and low risk of VTE will provide an important precision tool that could be combined with existing tools to guide therapy and improve outcomes. Results from aim 2 will provide key preliminary data in support of novel antiplatelet treatments to limit cancer progression.


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 = $0 )
2025	2023	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT STREET	BURLINGTON	VT	05405	CHITTENDEN	USA	Cancer Detection and Diagnosis Research	000	2	3/28/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $214,414 )
2023	2023	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT ST	BURLINGTON	VT	05405	CHITTENDEN	USA	Cancer Detection and Diagnosis Research	000	2	2/2/2023	NON-COMPETING CONTINUATION	$214,414
														Subtotal = $214,414

Issue Date FY: 2022 ( Subtotal = $182,325 )
2022	2022	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT ST	BURLINGTON	VT	05405	CHITTENDEN	USA	Cancer Detection and Diagnosis Research	000	1	11/23/2021	NEW	$182,325
														Subtotal = $182,325

Grand Total All Awards = $396,739

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Platelet FcGammaRIIa and Risk of Venous Thromboembolism in Cancer

Award Number: R21CA267074

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2025

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