CO-116: A Metal-Free Carbon Monoxide Prodrug Shows Promise in Suppressing Metastatic Cancer
Study Overview
A study published in Advanced Science reports that a metal-free carbon monoxide prodrug, known as CO-116, significantly reduced metastatic tumor growth in mouse models of pancreatic and triple-negative breast cancer. The research was led by scientists at Weill Cornell Medicine and Georgia State University.
"The approach uses a metal-free prodrug to release controlled carbon monoxide levels."
Key Findings
- How it works: CO-116 is a prodrug designed to release low, controlled levels of carbon monoxide after intravenous administration.
- Significant results: In multiple mouse models, treatment with CO-116 significantly reduced the growth of metastatic tumors in the liver and lungs.
- Safety profile: This was achieved without signs of toxicity, weight loss, or behavioral changes.
- Dosing strategy: Administering smaller doses more frequently was more effective than the same total amount given as a single larger weekly dose.
Mechanism of Action
- Targeting HRG1: CO-116 reduces levels of HRG1, a protein involved in heme import by cancer cells.
- Disrupting metastasis: Lowering HRG1 disrupts a signaling pathway that promotes cancer cell migration and metastatic growth.
- Genetic link: Genetic manipulation of HRG1 levels directly affected cancer cell aggressiveness and responsiveness to CO-116.
Background
This research builds on a prior 2022 study by the same team, which indicated that low-dose carbon monoxide hindered metastasis in preclinical models. However, earlier delivery methods—such as inhaled gas or metal-containing molecules—faced safety or toxicity issues.
CO-116 is metal-free, avoiding the toxic byproducts associated with previous carbon monoxide delivery systems.
Limitations and Next Steps
- Not yet for patients: The therapy is not yet ready for patient testing.
- Future research needed: Studies must evaluate long-term safety, optimal dosing schedules, and the durability of antimetastatic effects.
- Potential biomarker: HRG1 may serve as a therapeutic target or biomarker for selecting patients most likely to benefit from this treatment.
First author Tiantian Zhang noted that dosing frequency may be more important than total dose when using this approach.