# A Novel Assay to Individualize Resensitization of Iodine-Refractory Thyroid Cancer

> **NIH NIH R61** · STANFORD UNIVERSITY · 2023 · $216,862

## Abstract

Abstract
Thyroid cancer patients with distant metastases or unresectable disease have poor likelihood of long-term
survival. Radioactive iodine (RAI) can specifically and systemically eradicate malignant thyroid cancer cells that
have spread throughout the body through metastasis. However, 5-15% of all thyroid cancer patients eventually
progress to RAI-refractory status, which has the poorest prognosis of all thyroid cancer cases. Refractory disease
occurs when thyroid tumor cells lose their innate ability to take up and concentrate RAI. Recent clinical studies
have shown that kinase inhibitors and other drugs can reverse this effect by redifferentiating refractory tumor
cells, thus restoring the cellular machinery required to concentrate RAI. However, this redifferentiation strategy
remains challenging to optimize and deploy clinically. The reasons for this include the small number of patients
eligible, the heterogeneity of the disease, the toxicity of targeted kinase therapies, and the lack of robust
biomarkers. This project will develop papillary thyroid carcinoma organoids to study and individualize the use of
redifferentiation agents to restore RAI uptake in RAI-refractory patients. In the first Aim, we develop a novel
automated and high-throughput assay to measure RAI uptake in thousands of tumor organoid cultures. The
assay will be optimized to achieve specific performance goals, including throughput, linearity, limit of detection,
and reproducibility. In the second Aim, we will demonstrate the assay in a small pilot study of 10 patients. The
panel of tumor organoids, which will include both RAI-sensitive and refractory disease, will be used to screen a
library of relevant drugs on the basis of RAI uptake. Using the approach, we will optimize dosing and scheduling
of the treatments towards the eventual goal of individualizing therapy to maximize efficacy while minimizing the
adverse side effects of kinase inhibitors.

## Key facts

- **NIH application ID:** 10612661
- **Project number:** 1R61CA278459-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Guillem Pratx
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $216,862
- **Award type:** 1
- **Project period:** 2023-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10612661

## Citation

> US National Institutes of Health, RePORTER application 10612661, A Novel Assay to Individualize Resensitization of Iodine-Refractory Thyroid Cancer (1R61CA278459-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10612661. Licensed CC0.

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