Two pronged approach to melanomas shows promise

An international team of researchers have developed a new substance which uses a two pronged attack on malignant cells.

The substance, a single 'designer molecule' plays it safe and fights malignant melanomas by two completely different routes - on the one hand, the substance is similar to components of viruses and in this way alerts the immune system, strengthening in the process the body's own defences against cancer - and at the same time, the novel molecule also puts pressure on the tumour in a different way by switching off a specific gene in the malignant cells and driving them to suicide.

The researchers led by Professor Thomas Tüting from the University of Bonn conducted a study on specially bred mice, suffering from cancer and were able to fight metastases in the lung.

Their research project used the most up to date research on a relative of the nuclear DNA, known as RNA, and used them as therapy.

It has only been known for a few years that small RNA molecules can basically be used to target certain genes and switch them off, an effect called RNA interference for which U.S. scientists Craig Mellow and Andrew Fire were awarded the Nobel Prize in 2006.

Dermatology researcher Professor Tüting says they used this method to drive the tumour cells to suicide - he says every single body cell is equipped with a corresponding suicide programme which is activated, for example, if the cell becomes malignant - and the cell dies before it can do any more harm.

Professor Tüting, who is head of the Experimental Dermatology Laboratory, says in tumours a gene is active that suppresses this suicide programme and they have pinpointed this gene and switched it off by using RNA interference.

The researchers simultaneously attacked the cancer by another route; Professor Gunther Hartmann, director of the Institute of Clinical Chemistry and Pharmacology says they "disguised" the RNA, which is why the immune system took it for the genetic makeup of a virus.

Professor Hartmann says many viruses use RNA to store information, so if the body discovers RNA fragments which it takes to be the genetic makeup of a virus, it mounts an attack on them and tricks the body's defences into tackling the tumour cells far more aggressively than normal.

Professor Hartmann says RNA is also present in the body's own cells and for a long time it was not known how the immune system distinguishes between 'harmful' and 'harmless' RNA but two years ago he resolved this and that knowledge was used in order to modify the RNA substance in such a way that it was able to alert the immune system.

Professor Hartmann says the beauty of the method is that the cancer can be attacked with one designer molecule along two completely different routes, which deprives the tumour of opportunities of sidestepping the attack which makes successful therapy so difficult.

The researchers found in their initial experiments with mice, that the growth of cancers in the lungs is inhibited significantly by the new molecule and also that secondary tumours became smaller or even disappeared completely.

However the research team warns that while the approach appears very promising, especially as the therapeutic RNA molecule can be easily customised to suit different kinds of cancer, what works in mice does not necessarily prove successful in humans as well and they say many issues need to be addressed before a trial with cancer patients can be considered.

The research is published in the current issue of Nature Medicine.