Cancers: a common weak point discovered – here’s how to target them without damaging healthy cells
A study by Weill Cornell Medicine has identified a vulnerability present in a wide range of cancers. The first compound works in the laboratory, but there is still a long way to go before it reaches patients
Key points
A weakness shared by many cancers could become the target of a new generation of therapies with fewer side effects. This is suggested by a study recently published in Nature Chemical Biology by researchers at Weill Cornell Medicine in New York, the medical school of Cornell University.
The target is the so-called Wnt pathway, a signalling system that transmits signals from outside the cell to inside it. In tumours, it is often overactive and promotes malignant growth through several mechanisms. According to the authors, this abnormality is present in almost all colorectal cancers, in more than half of breast cancers, and in a significant proportion of cancers of the liver, lung, prostate, skin, bone and the female reproductive system.
A problem that goes back decades
Targeting the Wnt pathway has long been a focus of cancer research, but the problem is that this system is also essential for healthy cells. One approach previously investigated targeted two enzymes, known as tankyrases (TnkS1 and TnkS2), which sustain the signal. The experimental inhibitors, however, also damaged normal tissues: in early clinical trials, they caused side effects that limited the doses that could be used.
The discovery, made by chance
The team led by Lukas Dow, Professor of Biochemistry in Medicine, has found a different approach. “We stumbled upon this by chance,” says Dow: whilst studying the two enzymes separately, the researchers noticed that in some cancer cells, simply switching off TnkS2 was enough to reduce the Wnt signal.
The explanation lies in the DNA. During their development, most tumours undergo extensive deletions of genetic material, and one of the most common deletions removes the TnkS1 gene. This does not cause immediate harm to the tumour cell, because TnkS2 performs the same function. However, it does make the cell dependent on a single enzyme. A drug that blocks only TnkS2 could therefore weaken or kill the diseased cells, whilst leaving healthy cells – which still possess both enzymes – unharmed.
