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An Investigation of the Molecular Mechanisms for and Prediction of the Severity of Cancer Chemotherapy-Related Fatigue Using a Multi-staged Integrated Omics Approach

Award Number: R37CA233774
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/03/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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An Investigation of the Molecular Mechanisms for and Prediction of the Severity of Cancer Chemotherapy-Related Fatigue Using a Multi-staged Integrated Omics Approach - PROJECT SUMMARY Cancer-related fatigue (CRF) is the most common symptom associated with cancer and its treatments. Moderate to severe CRF has a negative impact on patients' ability to tolerate treatments as well as on their quality of life. In some patients, CRF is so severe, that they discontinue cancer treatment. Given its high occurrence and significant negative impact, it is imperative that effective treatments be developed for this devastating symptom. Two of the major knowledge gaps for CRF are a lack of a risk prediction model and a lack of knowledge of its underlying mechanisms. A sensitive and specific risk prediction model would assist clinicians to determine which patients are most likely to experience high levels of CRF and provide recommendations regarding activity modifying interventions (e.g., exercise). Increased knowledge of the mechanisms for CRF could identify potential targets for therapeutic interventions. Both of these knowledge gaps will be addressed in this application. Prior studies suggest that patients will experience an increase in the severity of CRF in the weeks following concurrent chemotherapy and radiation therapy (CCRT) that can persist after completion of treatment. However, no models exist to predict the magnitude of this increase. This inability to predict the severity of CRF during and following CCRT limits the ability of clinicians to identify high-risk patients and provide them with recommendations to manage CRF. To address this knowledge gap, demographic, clinical, and molecular data that are collected prior to the initiation of CCRT will be used to evaluate the utility of these features to predict the severity of CRF midway through, at the completion of, and six months following the completion of CCRT. In terms of mechanisms of CRF, while previous studies provide some insights into potential mechanisms that underlie CRF, several limitations warrant consideration, including: poorly defined CRF phenotype; relatively small sample sizes; evaluation of patients receiving only CTX or only RT; evaluation of a single type of molecular data; and evaluation of only cross-sectional molecular data. To address these limitations, we propose to evaluate for associations between changes in CRF and changes in gene expression and circulating cytokines in patients receiving CCRT over two time points (i.e., prior to and at the completion of treatment). This study will provide new insights to be able to identify high-risk patients as well as identify potential therapeutic targets. This project will guide the development of clinical studies to investigate additional mechanisms and therapeutic interventions for CRF and other types of fatigue associated with cancer and its treatment (e.g., immunotherapy, surgery).


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 = $657,307 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Treatment Research	003	7	6/18/2025	NON-COMPETING CONTINUATION	$657,307
2025	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Treatment Research	001	6	2/28/2025	EXTENSION WITH OR WITHOUT FUNDS	$76,007
2025	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Treatment Research	000	5	2/28/2025	NON-COMPETING CONTINUATION	-$55,005
2025	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Treatment Research	002	5	2/28/2025	SUPPLEMENT FOR EXPANSION	-$21,002
														Subtotal = $657,307

Issue Date FY: 2024 ( Subtotal = $624,441 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Treatment Research	000	6	7/9/2024	EXTENSION WITH OR WITHOUT FUNDS	$624,441
														Subtotal = $624,441

Issue Date FY: 2023 ( Subtotal = $876,539 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Treatment Research	001	5	9/6/2023	SUPPLEMENT FOR EXPANSION	$242,197
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Treatment Research	000	5	6/23/2023	NON-COMPETING CONTINUATION	$634,342
														Subtotal = $876,539

Issue Date FY: 2022 ( Subtotal = $726,492 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Treatment Research	001	4	7/18/2022	SUPPLEMENT FOR EXPANSION	$75,878
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Treatment Research	000	4	7/1/2022	NON-COMPETING CONTINUATION	$650,614
														Subtotal = $726,492

Issue Date FY: 2021 ( Subtotal = $653,863 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Treatment Research	000	3	6/15/2021	NON-COMPETING CONTINUATION	$653,863
														Subtotal = $653,863

Issue Date FY: 2020 ( Subtotal = $644,495 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Treatment Research	000	2	6/29/2020	NON-COMPETING CONTINUATION	$644,495
														Subtotal = $644,495

Issue Date FY: 2019 ( Subtotal = $625,752 )
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Treatment Research	000	1	7/3/2019	NEW	$625,752
														Subtotal = $625,752

Grand Total All Awards = $4,808,889

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An Investigation of the Molecular Mechanisms for and Prediction of the Severity of Cancer Chemotherapy-Related Fatigue Using a Multi-staged Integrated Omics Approach

Award Number: R37CA233774

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/03/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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