US scientists devise strategy to block key cancer molecule

Researchers in the US may have discovered a way to switch off the cancer-causing effects of a molecule called NF-κB.

Unlike previous attempts, the new method appears to leave its normal role in cell growth, immunity and inflammation unaffected.

The discovery, made in labs at the University of Illinois, could ultimately help towards new approaches to treat a range of cancers.

NF-κB plays a key role in the immune system. But its active form has been detected in the ‘control centre’ – the nucleus – of various types of cancer cell, and appears to help drive cancer’s growth. Quite how it gets there, and what keeps it active, has been a mystery.

According to University of Illinois’s Professor Lin-Feng Chen, who led the new study: “Normally NF-κB is not in the nucleus, and it’s not activated. You have to stimulate normal cells to see NF-κB in the nucleus.”

But in cancer cells, says Chen, the active form of NF-κB can be detected in the nucleus without any external stimulus.

“The cell just won’t die because of this. That is why NF-κB is so important in cancer,” he adds. Because of this, researchers have considered NF-κB a good target for new cancer drugs.

But previous attempts to target NF-κB have been mixed and have caused serious side effects, says Professor Neil Perkins, a Cancer Research UK NF-κB expert based in Newcastle, who wasn’t involved in the research.

“This is because NF-κB is both a ‘bad cop’ and a ‘good cop’, as while it can cause cancers to grow, some normal cells also require it for their survival, and it is needed in the immune response following infection. So totally inhibiting NF-κB can cause big problems,” he added.

In the new study published in the journal Oncogene, the Illinois researchers focused on whether blocking the action of a second molecule, called BRD4, could prevented NF-κB from being activated.

The scientists exposed lung cancer cells grown in the laboratory, and in immune-deficient mice, to an experimental drug that interferes with BRD4 activity, called JQ1.

They showed that JQ1 blocked the interaction of BRD4 and NF-κB, stopping it switch on genes involved in cancer.

This both slowed the growth of lung cancer cells, and reduced their ability of to form tumours in immune-deficient mice.

Professor Perkins says it’s important but early-stage work: “It’s exciting that the researchers seem to have found a different way to inhibit it and cut off NF-κB’s ‘bad cop’ characteristics, by targeting one of its cellular partners”.

“The bulk of this work is only in cells in the lab. Further research is needed to see if drugs like JQ1 could be used to block NFκB, and treat cancer, in people,” he added.

Copyright Press Association 2013