Wednesday, January 7, 2026 1/7/2026

Chemotherapy-induced circadian master clock disruptions and fatigue

Award Number: R01CA270372
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/23/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2027

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Chemotherapy-induced circadian master clock disruptions and fatigue - PROJECT SUMMARY/ABSTRACT Understanding the causes and mechanisms underlying circadian rhythm disruptions that are associated with fatigue during cancer treatment remains unclear. This current deficiency means that successful cancer treat- ment falls short of its potential and prior quality-of-life remains elusive for patients. Our long-term goal is to im- prove debilitating behavioral sequelae in cancer patients, thus improving quality-of-life, other comorbidities, and mortality. Thus, the overall objective here is to establish the potential role of circadian disruption as a fun- damental pathway by which chemotherapy promotes cancer-associated fatigue. Indeed, robust circadian rhyth- micity of virtually all physiology is extremely well-conserved; desynchrony of these rhythms leads to negative health and behavioral consequences. The central hypothesis is that chemotherapy-induced inflammation inhib- its SCN function leading to fatigue. The rationale for this work is that circadian circuitry disruption is an under- studied, relevant pathway in psycho-oncology research that could elucidate mechanisms and new, rhythm-fo- cused interventions. Three specific aims are proposed to test the central hypothesis using our novel breast cancer “survivor” mouse model. Aim 1 will determine the ability of the master clock to entrain after chemother- apy. Behavioral SCN rhythm adaptations to environmental challenges will be assessed. Aim 2 will identify the role of central inflammation in master clock disruptions after chemotherapy. The role of chemotherapy-induced neuroinflammation on SCN molecular and behavioral rhythms will be quantified. The potential resolution of fa- tigue will also be assessed. Aim 3 will determine the role of circadian disruption in chemotherapy-induced fa- tigue. Genetic and pharmacological SCN timing manipulations will precede a battery of behavioral assess- ments of the physical, motivation, and cognitive components of fatigue. In vivo and ex vivo circadian timing ap- proaches combined with systems-, cellular-, and molecular-level analyses will pinpoint the effects of two regi- mens of chemotherapy on master oscillator circadian circuitry relevant to cancer-related behavioral comorbidi- ties. The proposed research is conceptually innovative because using circadian approaches is new to psycho- oncology. It is also technically innovative by way of the superior translational model and the circadian genetic and pharmacological techniques planned. This research will result in essential new knowledge about how com- mon cancer treatments affect the pacemaker, which is crucial to extensive downstream physiology and behav- ior (i.e., beyond fatigue). Results will provide much needed evidence to make circadian-based approaches standard in clinical practice, as well as inform the design of novel circadian-directed pharmacological and non- pharmacological interventions. This research is applicable to other cancers and in non-oncological populations treated with chemotherapy (e.g., stem cell transplant, lupus).


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: 2026 ( Subtotal = $464,593 )
2026	2026	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Treatment Research	000	4	12/18/2025	NON-COMPETING CONTINUATION	$464,593
														Subtotal = $464,593

Issue Date FY: 2025 ( Subtotal = $609,412 )
2025	2025	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Treatment Research	001	3	12/5/2024	SUPPLEMENT FOR EXPANSION	$72,094
2025	2025	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Treatment Research	003	3	9/12/2025	SUPPLEMENT FOR EXPANSION	$8,011
2025	2025	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Treatment Research	002	3	6/23/2025	NON-COMPETING CONTINUATION	$52,930
2025	2025	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Treatment Research	000	3	12/3/2024	NON-COMPETING CONTINUATION	$476,377
														Subtotal = $609,412

Issue Date FY: 2024 ( Subtotal = $583,537 )
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Treatment Research	002	2	4/16/2024	NON-COMPETING CONTINUATION	$26,706
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Treatment Research	001	2	1/30/2024	SUPPLEMENT FOR EXPANSION	$72,094
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Treatment Research	000	2	12/13/2023	NON-COMPETING CONTINUATION	$480,732
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Treatment Research	003	2	4/16/2024	SUPPLEMENT FOR EXPANSION	$4,005
														Subtotal = $583,537

Issue Date FY: 2023 ( Subtotal = $579,659 )
2023	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Treatment Research	001	1	7/19/2023	SUPPLEMENT FOR EXPANSION	$31,509
2023	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Treatment Research	000	1	1/22/2023	NEW	$548,150
														Subtotal = $579,659

Grand Total All Awards = $2,237,201

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Chemotherapy-induced circadian master clock disruptions and fatigue

Award Number: R01CA270372

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/23/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2027

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