Scientists decode cancer's secret signals

Cancer Research UK

Experts funded by Cancer Research UK have identified four new molecules, which they believe may hold the key to halting the rapid spread of lung cancer.

Dr Michael Seckl and his team at Imperial College and Hammersmith Hospital, London, are investigating small cell lung cancer (SCLC), a particularly fast growing form of the disease. It affects around 10,000 people each year in the UK. It is notoriously difficult to treat and often becomes resistant to chemotherapy.

In a paper published in the Journal of Biological Chemistry1, Dr Seckl's team have identified vital molecules that help the disease grow and resist treatment. The researchers hope that their findings will open the way to designing more effective drugs, which are urgently needed.

Dr Seckl says: "There's a desperate need for new treatments for lung cancers. This type of tumour grows incredibly fast and many patients are diagnosed when the disease is already widespread. Surgery is rarely an option, so we usually treat lung cancer patients using combinations of chemotherapy and radiotherapy.

"Often the disease seems to disappear, and when we examine the scans they look clear. But in fact the cancer is still there - just too small to detect. And within months it rears its ugly head again, and this time it's resistant to further treatment. It's terribly dispiriting for patient and doctor."

Dr Seckl's team have taken their research back to basic cell biology, investigating the mechanisms that the cancer cell uses to grow, spread and resist current treatments. They have concentrated their efforts on a growth factor known as FGF-2. Growth factors work by latching on to tiny receptors on the outside of the cell and setting off a chain of signals to the cell's nucleus - its command centre - instructing it to make the cell grow and divide.

Dr Seckl says: "We knew that FGF-2 was ten to twenty times higher in the blood of patients with cancer than healthy people. We now believe that FGF-2 uses a double action - promoting cancer cell growth and making it resistant to chemotherapy.

He explains: "It works in two ways. Firstly it activates two other molecules called S6K1 and S6K2. These send signals to the cell telling it to divide. The cell quickly grows out of control, eventually forming a tumour.

"Secondly it uses another signalling molecule, MEK, to counter the effect of anticancer drugs. And drug resistance is the main reason why so many patients die from the disease.

"All four molecules are targets for new drugs that will block cancer growth and restore its sensitivity to existing treatments. Our aim now is to design and develop these new drugs."

Professor Gordon McVie, Joint Director General of Cancer Research UK, says: "Dr Seckl's work is at the forefront of research into small cell lung cancer. Resistance to treatment is a major problem we are yet to overcome.

He adds: "Dr Seckl's discoveries add vital pieces to the jigsaw of our understanding of this particularly nasty form of the disease. We now need to push on to find new drugs that will target these key molecules, stopping the cancer dead in its tracks."

Sir Paul Nurse, Joint Director General of Cancer Research UK says: "Cancer Research UK is committed to improving quality of life and survival for people with lung cancer. We believe that at Cancer Research UK we will be able to take potential new targets like these molecules, and turn them into effective treatments for cancer patients faster than before."

Lung cancer, dubbed the 'invisible cancer' is the single biggest killer cancer in the UK. Only five per cent of the 40,000 people diagnosed in the UK each year survive the disease beyond five years.

ENDS

  1. Journal of Biological Chemistry (April 2002) 277

Notes to Editor

There were more than 38,000 cases of lung cancer diagnosed in the UK in 1997.

In 1999, lung cancer claimed over 34,200 lives, making it the most common cause of cancer death in the UK.

Small cell lung cancers account for around a quarter of cases diagnosed.

Lung cancer has one of the lowest survival rates for any cancer. Around 20 percent of patients are alive one year after diagnosis and this falls to 5 percent at five years.

Resistance in lung cancer: All cells have a natural suicide mechanism, called apoptosis, which should kick in if the cell becomes damaged or grows out of control. In cancer this suicide mechanism is faulty or suppressed and so the cancer cell survives. The main drug used to treat SCLC is called etoposide, and it works by harnessing the apoptosis mechanism, encouraging the cancer cells to commit suicide. Resistance to drugs like etoposide is the main reason why patients die from SCLC. Dr Seckl's group have discovered that FGF-2 uses another critical signalling molecule, MEK, to bypass etoposide and stop this natural cell suicide from taking place.