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Blocking cancer

Blocking cancer CANCER patients at a hospital in Edinburgh are being treated with a drug that gums up the molecular :ccelerator pedals' on the surface of tumour cells. Blocking these sites could halt the growth of tumour cells, so that they wither and die. The drug is designed to treat small-celllung cancer, which often effects smokers and accounts for one in four lung cancer cases, killing 10,000 people each year in Britain (New Scientist, Vo1150, No 2026). "I think the approach we are taking is unique," says Enrique Rozengurt, head of the team at the Imperial Cancer Research Fund (ICRF).

Most anti-cancer agents recognise and kill cancer cells because they divide faster than normal cells. But some healthy cells divide quickly, too, and are caught in the crossfire, causing distressing side effects. Also, any drug-resistant tumour cells will regrow. So, follow-up treatment with the same drugs will not eradicate these cells.

The new drug developed at the ICRF works in a completely different way. The drug does not destroy fast-growing cells but blocks the molecular messages that tell the cells to proliferate, breaking a vicious circle that makes small-celllung tumours grow explosively.

Cells in these cancers secrete abnormally high amounts of growth-factor hormones, called neuropeptides. When these hormones lock onto surface receptors on the same or the neighboring cancer cells, they tell the cells to grow and divide faster, churning out yet more growth factor. The ICRP'S drug occupies the sites on the surface of the cancer cells and breaks the vicious circle. What makes the drug very special is that it blocks receptors for several different growth factors.

Rozengurt found that tumour cells in small-cell lung cancer secrete and respond to a variety of growth factors, including vasopressin (an anti-diuretic) and gastrin-releasing peptide (a hormone that regulates digestion). They all accelerate growth, so only by gumming up the receptor sites for all of them can the tumour cell be tamed.

The drug is a synthetic peptide that is similar in structure to the naturally occurring neuro-transmitter called 'substance p', which transmits pain sig- nals. It was initially developed to block 'substance p' receptors. Rozengurt and his colleagues found that it blocks several neuro-transmitters as well.

The drug occupies 'serpentine receptors' that breach the surface of the cell at several points to resemble the humps of a sea serpent. Although recep- tors for each neuropeptide are subtly different, the ICRF drug somehow occupies them all.

Patients at the ICRF'S medical oncology unit at the Western General Hospital in Edinburgh have begun receiving the drug in a programme. The aim of the initial trials is not to cure people, but to establish safe dosages.

Although normal cells produce and respond to growth factors, Rozengurt expects the cancer cells to be uniquely sensitive to the drug because their survival depends on them. If the drug works, he expects it will be used after orthodox chemotherapy has neutralised most tumour cells.

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