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Clonal hematopoiesis and therapy-emergent myeloid neoplasms in patients with ovarian cancer

Award Number: R01CA272594
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2023
PERIOD OF PERFORMANCE END DATE: 04/30/2028

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Clonal hematopoiesis and therapy-emergent myeloid neoplasms in patients with ovarian cancer - ABSTRACT Most women diagnosed with ovarian cancer are treated with many rounds of chemotherapy and often years of a an oral PARP inhibitor drug for “maintenance” therapy. These therapies have extended life for women with metastatic ovarian cancer, but at the cost of increased toxicity. One long term toxicity is the development of leukemia or other blood disorders, often called therapy related myeloid neoplasia (TMN). These secondary malignancies are a known risk of chemotherapy, and ovarian cancer survivors have one of the highest rates of TMN of any group of cancer survivors. The diagnosis of TMN is usually fatal, with survival measured in months. TMN is nearly always detectable in a pre-malignant state as a clonal expansion of blood cells years before a clinical diagnosis. Non-malignant clonal expansion of white blood cells is often termed clonal hematopoiesis of indeterminate potential (CHIP). The interval between CHIP and development of blood cancers is many years, providing an opportunity to better understand the natural progression of TMN and perhaps a window for intervention and prevention. Clonal hematopoiesis (CH) can also arise during normal aging, but only a small fraction progress to a blood cancer. A better understanding of the natural progression of CH in ovarian cancer survivors is needed to tailor safe and effective ovarian cancer therapies. Our team is co-led by experts in ovarian cancer genetics and hematological malignancies and will enroll 2000 survivors across the country with ovarian cancer, including 200 with CH. We will follow these individuals with CH with serial blood draws obtained every 6 months for at least 3 years to define risk factors for progression of CH to TMN. For a subset of patients with acquisition of TMN during the study, we will evaluate clonal dynamics and genetic and chromosomal alterations over time at the single cell level, which will provide novel data on the changes that occur in the malignant transformation of myeloid cells in response to cytotoxic therapy. In this way, we will learn who is at risk of TMN and develop strategies for the monitoring and prevention of this deadly long-term treatment toxicity. These studies will improve outcomes for patients with ovarian cancer and also will be applicable to survivors or many cancer types, who are also at risk for TMN.


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 = $648,957 )
2025	2025	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Cancer Cause and Prevention Research	000	3	4/25/2025	NON-COMPETING CONTINUATION	$584,062
2025	2025	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Cancer Cause and Prevention Research	001	3	5/22/2025	NON-COMPETING CONTINUATION	$64,895
														Subtotal = $648,957

Issue Date FY: 2024 ( Subtotal = $616,508 )
2024	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Cancer Cause and Prevention Research	000	2	4/22/2024	NON-COMPETING CONTINUATION	$616,508
														Subtotal = $616,508

Issue Date FY: 2023 ( Subtotal = $648,956 )
2023	2023	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Cancer Cause and Prevention Research	000	1	4/27/2023	NEW	$648,956
														Subtotal = $648,956

Grand Total All Awards = $1,914,421

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Clonal hematopoiesis and therapy-emergent myeloid neoplasms in patients with ovarian cancer

Award Number: R01CA272594

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2023

PERIOD OF PERFORMANCE END DATE: 04/30/2028

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