Switching Off Cancer at Its Source

 

Cancer can begin with a simple mistake: the wrong genes being switched on at the wrong time. Inside our cells, chemical tags known as epigenetic modifications, such as histone acetylation, act like switches that control gene activity. When these switches malfunction, they can drive tumour growth.

Our research team has developed a new way to turn those switches off.

The team focused on the ATAC complex, a key regulator that activates cancer-related genes. Previous efforts to stop these cancer-promoting signals targeted its enzymatic subunit, GCN5, within the ATAC complex. However, GCN5 is also used by other essential cellular complexes, meaning such approaches could disrupt normal cell functions.

To overcome this, our researchers took a more precise route.

They designed and developed a first-in-class inhibitor, LS-170, which blocks YEATS2, a component unique to the ATAC complex. This allows the drug to selectively shut down cancer-driving signals without broadly affecting healthy cellular processes.

In laboratory studies and animal models of non-small cell lung cancer, LS-170 significantly suppressed tumour growth and spread. As the YEATS2 gene is also amplified in other cancers, including ovarian and pancreatic tumours, the approach may have wider therapeutic potential.

The study points to a new direction in epigenetic drug design, one that aims to treat cancer by precisely controlling the genetic switches that drive it.

 

ATAC 複合物負責調控組蛋白乙醯化，屬於控制基因開關的重要機制；當其異常活化時，會促進致癌基因表達。過去研究多針對其核心酵素 GCN5，但由於該酵素同時存在於其他正常細胞複合物，容易影響正常功能。

 

本研究改為鎖定 ATAC 特有的 YEATS2 蛋白，大幅提升抑制的選擇性。實驗結果顯示，LS-170 能有效抑制腫瘤生長及擴散，為非小細胞肺癌提供嶄新治療方向，並有潛力應用於多種癌症。