Why lung cancer resists treatment

Main Category: Lung Cancer
Article Date: 22 Nov 2003 - 0:00 PDT


Lung cancer is one of the hardest to treat - but scientists may have found out how it shakes off the effects of powerful chemotherapy.

Recent figures show that only one in 20 lung cancer patients survives beyond five years.

This is because cells launch a two-stage 'survival plan' when confronted with anti-cancer drugs, say experts from Imperial College London.

The finding could help them come up better ways to eradicate lung cancer.

The Imperial team, led by Professor Michael Seckl, is looking at small cell lung cancer, a particularly 'hard-to-treat' form of the disease.

All normal cells have a programmed 'suicide' mechanism, which kicks in if the cell is getting too old, or is damaged in some way.

Cancer cells in general are different, because despite their age, they do not 'commit suicide'.

Drug resistance

Many anti-cancer drugs aim to trigger this programmed cell death function, and in many cancers, this is remarkably effective.

At first, against small cell lung cancer, a drug called etoposide works well, but stops working very quickly as the cancer cells become resistant to it.

Professor Seckl's team has been investigating how the cells manage to acquire this ability.

They found that exposure to the drug activates a cascade of chemical reactions within the cancer cell that allows it to protect itself.

If releases a molecule called FGF-2 which shuts off the suicide mechanism.

This process also blocks the release of a molecule called Smac, which is also important to get the suicide mechanism working.

The double effect means that to get the suicide process working efficiently, it would have to be restarted at two separate points.

However, the research now means that a common trigger for both shutdown mechanisms has been found - in future, drugs could be designed to target it.

Professor Seckl said: 'Initially anti-cancer drugs can be effective, but the disease often returns in a form which is very resistant to further treatment.

'It's a huge stumbling block in the effective treatment of lung cancer.

'We knew this FGF-2 was found in much higher levels in the blood of people with cancer. The cancer cells use this molecule to protect themselves from chemotherapy and ensure their survival.

'By blocking its effects we can force cancer cells to commit suicide and restore their sensitivity to anti-cancer drugs.'

Professor Robert Souhami, from Cancer Research UK, which funded the trial, said: 'The major obstacle to treating small cell lung cancer is the resistance the disease develops to chemotherapy.

'Finding the molecular basis to this is vital in order to develop new drugs and improve survival for patients.'

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