Monday, August 4, 2025 8/4/2025

Epigenetic Therapies - New Approaches

Award Number: P50CA254897
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/16/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Epigenetic Therapies - New Approaches - ABSTRACT (Overall) Epigenetics refers to stable gene expression patterns mediated by DNA methylation and/or chromatin remodeling and is involved in cellular identity and repression of spurious transcription, including from repetitive elements. Over the past 20 years, in work led in part by investigators in this application, epigenetic changes were recognized as important drivers of cancer formation, progression and resistance to therapy. This recognition, along with the reversible nature of the biochemical modifications required for epigenetics led to the field of Epigenetic Therapy, which aims to reprogram gene expression to achieve a therapeutic effect. This field, which started with DNA methyltransferase (DNMT) inhibitors, has grown to a dozen epigenetic targets and over 30 drugs in clinical trials. Four targets have made it to US-FDA approval (DNMTs, Histone Deacetylases (HDACs), EZH2 and Isocitrate Dehydrogenases) and tens of thousands of cancer patients benefit from this every year. With the identification of new targets and the recognition that epigenetics is involved in sensitivity and resistance to chemotherapy and immunotherapy, the clinical potential of epigenetic therapy has begun to be explored in earnest. There remain fundamental challenges, from the lack of robust biomarkers of activity, to the emergence of resistance, and to the unexplained divide in responses between hematologic malignancies and solid tumors. This SPORE application will address all of these challenges. The SPORE team consists of investigators who are pioneers in the fields of cancer epigenetics and epigenetic therapy and explores new epigenetic targets and combination strategies along with a robust biomarker analysis pipeline to identify patients likely to respond and pharmacodynamic markers of response. The team leverages a strong clinical and translational pipeline built through the Van Andel Institute Stand Up To Cancer Epigenetics Dream Team, which has conducted 14 epigenetic therapy clinical trials in the past few years, and is fully committed to the clinical trials proposed in this application. This Epigenetic Therapy SPORE encompasses four major themes: (i) Develop and test drugs against new epigenetic targets (Projects 1, 2), (ii) Mechanistic and translational studies of immunosensitization by epigenetic therapy (projects 1-3), (iii) Studies of drug combinations that enhance the efficacy of known epigenetic drugs (projects 1-3); and (iv) Biomarker studies to define sensitivity and resistance to epigenetic therapy in the clinic (all Projects). These themes will be addressed through 3 projects: (i) Cyclin Dependent Kinases as Epigenetic Therapy Targets; (ii) Epigenetic synergy between DNMT and EZH1/2 inhibitors; (iii) Linking epigenetic-therapy induction of inflammasome signaling to generation of a BRCAness phenotype. These projects will be supported by three cores (administrative, pathology, genomics) and a key goal will also be to mentor the next generation of Epigenetic Therapy investigators and support cutting-edge science through the Career Enhancement and Developmental Research Programs.


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 = $2,521,916 )
2025	2025	CORIELL INSTITUTE FOR MEDICAL RESEARCH, INC.	403 HADDON AVE	CAMDEN	NJ	08103	CAMDEN	USA	Cancer Centers Support Grants	000	5	7/7/2025	NON-COMPETING CONTINUATION	$2,521,916
														Subtotal = $2,521,916

Issue Date FY: 2024 ( Subtotal = $2,421,039 )
2024	2024	CORIELL INSTITUTE FOR MEDICAL RESEARCH, INC.	403 HADDON AVE	CAMDEN	NJ	08103	CAMDEN	USA	Cancer Centers Support Grants	000	4	7/16/2024	NON-COMPETING CONTINUATION	$2,421,039
														Subtotal = $2,421,039

Issue Date FY: 2023 ( Subtotal = $2,345,381 )
2023	2023	CORIELL INSTITUTE FOR MEDICAL RESEARCH INC	403 HADDON AVE	CAMDEN	NJ	08103	CAMDEN	USA	Cancer Centers Support Grants	001	3	7/12/2023	NON-COMPETING CONTINUATION	$2,345,381
2023	2022	CORIELL INSTITUTE FOR MEDICAL RESEARCH, INC.	403 HADDON AVE	CAMDEN	NJ	08103	CAMDEN	USA	Cancer Centers Support Grants	000	2	12/2/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,345,381

Issue Date FY: 2022 ( Subtotal = $2,345,381 )
2022	2022	CORIELL INSTITUTE FOR MEDICAL RESEARCH, INC.	403 HADDON AVE	CAMDEN	NJ	08103	CAMDEN	USA	Cancer Centers Support Grants	001	2	9/21/2022	NON-COMPETING CONTINUATION	$50,437
2022	2022	CORIELL INSTITUTE FOR MEDICAL RESEARCH, INC.	403 HADDON AVE	CAMDEN	NJ	08103	CAMDEN	USA	Cancer Centers Support Grants	000	2	9/1/2022	NON-COMPETING CONTINUATION	$2,294,944
														Subtotal = $2,345,381

Issue Date FY: 2021 ( Subtotal = $2,269,729 )
2021	2021	CORIELL INSTITUTE FOR MEDICAL RESEARCH, INC.	403 HADDON AVE	CAMDEN	NJ	08103	CAMDEN	USA	Cancer Centers Support Grants	001	1	8/30/2021	NEW	$0
2021	2021	CORIELL INSTITUTE FOR MEDICAL RESEARCH, INC.	403 HADDON AVE	CAMDEN	NJ	08103	CAMDEN	USA	Cancer Centers Support Grants	000	1	8/16/2021	NEW	$2,269,729
														Subtotal = $2,269,729

Grand Total All Awards = $11,903,446

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Epigenetic Therapies - New Approaches

Award Number: P50CA254897

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/16/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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