A breakthrough in targeted cancer therapy

What is STING and why it matters

When triggered, the STING pathway acts like a cellular alarm system, alerting the immune system to take action—particularly useful in targeting cancer cells. While drugs that activate STING have shown promise in cancer treatment, they carry significant risks if activated in healthy tissues, often leading to harmful side effects.

The challenge: Targeting tumours without harming healthy tissue

A major obstacle with STING-based therapies has been their lack of specificity. Activating this pathway throughout the body can cause widespread inflammation and damage to healthy organs.

The solution: A two-part 'Prodrug' system

To address this, researchers at the University of Cambridge created a two-part ‘prodrug’ system. The innovation involves two harmless components that only become active when they meet inside a tumour.

One of the components is “caged”—chemically locked to remain inactive until it encounters a tumour-specific enzyme called β-glucuronidase, which is typically absent in healthy tissues. Once unlocked, it reacts with the second component to form a potent STING activator.

How it works

The two molecules are designed to efficiently recognize and bind to each other. This ensures that the activation only occurs inside tumours where the enzyme is present.

“This is like sending two safe packages into the body that only unlock and combine when they meet the tumour's unique chemistry,” said Professor Gonçalo Bernardes, lead researcher from Cambridge’s Yusuf Hamied Department of Chemistry.

Results from animal models

Laboratory tests showed that the components were nearly inactive on their own. However, when exposed to tumour conditions in zebrafish and mouse models, the drug was activated specifically in cancerous tissues—sparing vital organs such as the liver, kidney, and heart.

The results were published in the journal Nature Chemistry.

A step forward in precision medicine

This approach represents a major step forward for STING-based cancer therapies, which have struggled with targeting precision. The simplicity of the chemical design means it avoids complex bioengineering, making it more practical for real-world applications.

Looking ahead

Beyond cancer treatment, researchers believe this approach could inspire a new generation of precision medicines, potentially applicable to a variety of diseases where targeted immune activation is beneficial.