# Assessment of hyperthermia-based multimodal approach for hepatic colorectal metastases

> **NIH NIH R01** · CEDARS-SINAI MEDICAL CENTER · 2023 · $443,574

## Abstract

ABSTRACT
Worldwide, colorectal cancer is responsible for approximately 0.4 million deaths annually, which represent
approximately 10% of all cancer deaths. The main cause of death in colorectal cancer patients is hepatic
metastasis. Although regional treatment options, including hyperthermic isolated hepatic perfusion (IHP) and
percutaneous IHP, offer the benefits of both aggressive local treatment and limited systemic toxicity, the
management of unresectable hepatic colorectal metastases remains a major unsolved issue and more
effective novel regimens are needed. During the grant period, we propose developing a novel treatment
strategy for hepatic colorectal metastases. Considering our previous studies, the combined treatment of
hyperthermia, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), and ferroptotic agent
synergistically induces cytotoxicity and effectively enhances the tumoricidal efficacy of subcutaneous
xenografts. In this grant application, we hypothesize that a combinatorial treatment of mild
hyperthermia, the biologic agent TRAIL, and the ferroptotic agent artesunate (ART) is effective in
treating unresectable hepatic colorectal metastases (HCM). The specific aims of this project are to (1)
elucidate the mechanism of synergistic anti-tumor efficacy caused by hyperthermia in combination with TRAIL
and ART treatment (HTA: hyperthermia + TRAIL + ART) in tumoroid models, and (2) investigate the preclinical
efficacy of this HTA treatment in humanized rat isolated hepatic perfusion (IHP) models. The proposed studies
for the first aim will establish tumoroid models with tumor tissues from patients with HCM and employ
biochemical and molecular techniques to investigate the cell death mechanism induced by synergistic effects
of the HTA treatment. For the second aim, we will develop humanized rat IHP models with tumor tissues from
patients with HCM and then evaluate the therapeutic advantage of the HTA treatment. We believe that the
successful outcome of this study will support the application of this multimodal approach to HCM.

## Key facts

- **NIH application ID:** 10517858
- **Project number:** 1R01CA265827-01A1
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** YONG JUN LEE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $443,574
- **Award type:** 1
- **Project period:** 2023-09-19 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10517858

## Citation

> US National Institutes of Health, RePORTER application 10517858, Assessment of hyperthermia-based multimodal approach for hepatic colorectal metastases (1R01CA265827-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10517858. Licensed CC0.

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