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Rational design of drug combinations to target chemotherapy resistance in high-grade serous ovarian cancer via metabolomic profiling of patient-derived organoids

Award Number: R03CA252674
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract This resistant disease rates women, metabolomics resistance, of algorithm To regulatory of organoids. identified therapies project aims to develop a novel, interdisciplinary framework for the designed reprogramming of drug- tumors towards a responsive state. This pilot will focus on high-grade serous ovarian cancer, a with up to 20% o patients being refractory to primary treatment with carboplatin, and 80% relapse of initially responsive patients. We will obtain primary tumor tissue rom 12 refractory and 12 responsive grow patient-derived organoids as a personalized in vitro model of the patients' tumors, and perform profiling on both tissue samples and organoids. This will allow us to identify metabolic states of which will pinpoint the molecular escape mechanisms resistant tumors employ to evade the action the chemotherapeutic agent. In the second phase of the project, we wil l develop a novel computational that predicts which other drug is most likely to reprogram the tumor into a carboplatin-sensitive state. this end, we will map the metabolic profiles of resistance onto an integrated metabolic, signaling and pathway map to then identify drugs whose targets are upstream of the desired effect. In the last part the project, we will choose the highest-scoring predictions and validate them experimentally on the Specifically, we expect to render resistant organoids responsive by pretreating them with the drugs. If successful, this project will establish a new paradigm for the rational design of combination in refractory tumors. f f


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 )
2025	2022	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Cancer Treatment Research	000	2	11/5/2024	NON-COMPETING CONTINUATION	-$2
														Subtotal = -$2

Issue Date FY: 2022 ( Subtotal = $84,750 )
2022	2022	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Treatment Research	000	2	6/30/2022	NON-COMPETING CONTINUATION	$84,750
														Subtotal = $84,750

Issue Date FY: 2021 ( Subtotal = $84,750 )
2021	2021	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Treatment Research	000	1	5/5/2021	NEW	$84,750
														Subtotal = $84,750

Grand Total All Awards = $169,498

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Rational design of drug combinations to target chemotherapy resistance in high-grade serous ovarian cancer via metabolomic profiling of patient-derived organoids

Award Number: R03CA252674

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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