ZJU researchers turn cancer cells’ own mistakes against them

Cancer cells are constantly working to grow and multiply, but their relentless activity can make them more prone to mistakes. Researchers at Zhejiang University have found a way to turn one such error into a potential weapon against cancer.

In a study published in Nature on November 4, a team led by researcher Mao Yuanhui from Zhejiang University School of Medicine and Liangzhu Laboratory reported the development of an engineered genetic circuit called FAST (frameshifting-activated synthetic therapeutic). The system exploits errors in protein production that occur more frequently in certain cancer cells, triggering a mechanism that causes them to destroy themselves.

Inside human cells, ribosomes act as molecular machines, reading genetic instructions to produce proteins. Normally, they follow a precise reading frame. Occasionally, however, a ribosome slips into a different reading frame, a phenomenon known as ribosomal frameshifting.

Metastasis observed in a mouse model of pancreatic cancer; the red areas represent fluorescently labeled metastatic cells.

The researchers discovered that certain genetic sequences trigger this process far more frequently in cancer cells than in normal cells. This led them to an intriguing question: Could these mistakes be turned into a way to selectively destroy cancer cells?

To explore this possibility, the team developed FAST, an artificial genetic circuit designed to exploit this difference. In normal cells, the system remains largely inactive. But in cancer cells with elevated frameshifting activity, it triggers the production of a protein that causes the cells to undergo a form of programmed cell death known as pyroptosis.

This process may also activate the immune system, helping the body recognize and attack cancer cells.

In laboratory and animal studies, FAST showed promising antitumor effects while largely sparing normal cells and tissues. The researchers also found that its efficacy could be enhanced when combined with existing cancer immunotherapies.

Unlike many conventional targeted therapies, which focus on specific genetic mutations or abnormal proteins, FAST takes a different approach. It exploits a vulnerability in the way cancer cells produce proteins, potentially offering a new strategy for treating different types of cancer.

Antitumor efficacy of FAST. Top: In a colorectal cancer mouse model, FAST alone or combined with anti-PD-L1 significantly inhibits tumor growth. Bottom: In a pancreatic cancer mouse model, FAST plus anti-PD-L1 reduces pancreas weight to near-normal levels, demonstrating potent antitumor efficacy.

The technology remains at the preclinical stage, and further research is needed to evaluate its safety and efficacy before it can be tested in patients.

Nevertheless, the findings open a promising new direction in cancer research: turning cancer cells’ own mistakes into a means of destroying them.

Adapted and translated from the article written by Yue Sicong
Photo: Ting Guang
Translator: Fang Fumin
Editor: Hu Chenyue