# A Patient-Centric Approach to Advance Functional Precision Oncology

> **NIH NIH U01** · FRED HUTCHINSON CANCER CENTER · 2024 · $1,007,878

## Abstract

PROJECT SUMMARY/ABSTRACT
The development of drug resistance is a major cause of cancer treatment failure and mortality. Although
much is known about the mechanisms by which tumor cells can become resistant to a given drug, translating
this into effective therapeutic solutions remains an unmet clinical need. Here we propose to pioneer the use
of patient derived tumor organoids (PDTOs) as a platform to identify and validate novel targets and effective
drugs to overcome drug resistance in ovarian cancer, pancreatic cancer, and other tumor types. In our
preliminary studies, we show that PDTOs genetically and phenotypically match the tumor from which they
were derived and can be used to study the phenotypic consequences of tumor heterogeneity, tumor
evolution, and drug resistance. Using a Clinical Laboratory Improvement Amendments (CLIA) approved
high complexity assay, we show that PDTO drug sensitivities are highly concordant with known genetic
biomarkers, retrospective treatment history and prospective patient responses. Tumor organoids derived
from patients who developed in situ drug resistance demonstrate ex vivo resistance to those same drugs but
also demonstrate sensitivity to other alternative oncology drugs. Additional preliminary studies show stable
disease or tumor regression in patients treated with drugs identified from organoid drug screens. Here, we
propose to combine drug screening and molecular profiling of PDTOs derived from a given patient from
different anatomic tumor sites and before and after therapy to elucidate the mechanistic basis for drug
sensitivity or resistance and to identify novel targets and effective drugs to treat metastatic, drug resistant
cancers. Accompanying computational prediction models that integrate large public datasets as well as
innovative methods of mechanistic target validation including CRISPR, targeted protein degradation
technologies, and epigenetic profiling, will be used to prioritize and advance targets and associated
biomarkers with greatest clinical potential. The rationale behind our approach is that identifying targets and
effective drugs directly in patient derived samples with known clinical history and outcomes will significantly
enhance translation of our findings. This proposal is significant because it will demonstrate the utility of
PDTOs as both a research tool for target discovery and validation but also as a clinically useful platform to
guide functional precision medicine. The findings and methods developed can be readily applied to other
cancer types and clinical challenges, will accelerate preclinical drug and drug target development, and will
translate to clinical studies. The models, approaches, and expected outcomes of this proposal are highly
responsive to the requirements of PAR-21-274.

## Key facts

- **NIH application ID:** 10933449
- **Project number:** 5U01CA282109-02
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** CHRISTOPHER J KEMP
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,007,878
- **Award type:** 5
- **Project period:** 2023-09-22 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10933449

## Citation

> US National Institutes of Health, RePORTER application 10933449, A Patient-Centric Approach to Advance Functional Precision Oncology (5U01CA282109-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10933449. Licensed CC0.

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