# Evaluating Novel Targeted Therapies in Cholangiocarcinoma Using Tumor Slice Cultures

> **NIH NIH R21** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $187,687

## Abstract

PROJECT SUMMARY/ABSTRACT
Intrahepatic cholangiocarcinoma (ICC) is a deadly liver cancer which has been rising in incidence over several
decades. The overarching goal of this proposal is to evaluate novel therapeutic strategies for the subset of ICC
harboring mutations in isocitrate dehydrogenase 1 (IDH1), the most common oncogenic driver in this disease.
In early phase clinical trials, pharmacologic inhibitors of mutant IDH provided clinical benefit in some patients,
but their mechanism of action remains poorly understood due to a paucity of on-treatment biopsy tissue and
relevant model systems. To overcome this hurdle, a protocol to maintain the viability and original architecture of
resected ICC tumors as `tumor slice cultures' (TSCs) and evaluate their response to targeted therapies within
their native microenvironment has been developed. In the proposal attached, 100 TSCs will be generated for
each of the ~50 resected ICCs over the next two years, anticipating 10-15 IDH mutant ICC tumors. We will then
assess their response to mutant IDH inhibition by monitoring proliferation, apoptosis, viability and the expression
of relevant biomarkers. Finally, we will evaluate possible combinatorial strategies based on top `hits' from
unbiased drug screens of IDH mutant preclinical models. Responses will be correlated with underlying tumor
genetics and compared to those of IDH wild-type tumors. Overall, these data will serve as proof of concept for a
long-term study exploiting ICC TSCs to elucidate the mechanisms underlying IDH inhibition in ICC, identify
predictive biomarkers of response and resistance and establish effective combinatorial strategies for subsequent
evaluation in a clinical trial setting.

## Key facts

- **NIH application ID:** 9857575
- **Project number:** 5R21CA231486-02
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Sita Kugel
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $187,687
- **Award type:** 5
- **Project period:** 2019-02-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857575

## Citation

> US National Institutes of Health, RePORTER application 9857575, Evaluating Novel Targeted Therapies in Cholangiocarcinoma Using Tumor Slice Cultures (5R21CA231486-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9857575. Licensed CC0.

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