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

> **NIH NIH R03** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $84,750

## Abstract

Project
Summary/Abstract
This
resistant
disease
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metabolomics
resistance,
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algorithm
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regulatory
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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.
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## Key facts

- **NIH application ID:** 10201800
- **Project number:** 1R03CA252674-01A1
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Jan Krumsiek
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $84,750
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201800

## Citation

> US National Institutes of Health, RePORTER application 10201800, Rational design of drug combinations to target chemotherapy resistance in high-grade serous ovarian cancer via metabolomic profiling of patient-derived organoids (1R03CA252674-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10201800. Licensed CC0.

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