29 March 2002 News Update

MIX AND MATCH DRUGS TO HIT CANCER

Doctors may soon "mix and match" anti-cancer drugs to find an ideal combination for attacking each particular type of tumour.

Scientists at Birmingham University, English Midlands, have gained detailed information about exactly how treatments send cancer cells to their deaths.

Professor Lawrence Young, who works for Cancer Research UK, and his team believe that by choosing a combination of drugs that are complementary to each other - each attacking cancer cells in different ways - should be an effective means of preventing tumours becoming resistant to treatment.

They have also managed to restore sensitivity to cancer cells that had already developed resistance by infecting them with a modified virus carrying a powerful suicide message. Anti-cancer drugs work by flicking on a "suicide switch'' in each cancer cell, with resistance developing when the switch becomes jammed. Professor Young's study reveals that the particular switch targeted varies from drug to drug.

The Birmingham team concentrated on ovarian cancer which often initially responds to chemotherapy only to later develop resistance against it. Professor Young removed cells from ovarian tumours, grew them in the laboratory and treated them with a range of anti cancer drugs.

After each treatment the researchers measured the levels and activity of a number of molecules that are involved in cell death. Depending on the drug used, they detected activation of different cell-death molecules, indicating that different ``suicide switches'' were being operated. They also found that some drugs were working through an unknown switch.

The team had previously thought that pushing cells to suicide required the presence of a cell-death molecule called Fadd. But although some drugs, such as fluorouracil and paclitaxel, were more effective in the presence of this molecule, others - including cisplatin and vincristine - were at least as effective in its absence.

Understanding more about this cell-death mechanism could help the future development of anti-cancer drugs. It is also hoped that by choosing drugs to target several different switches all at once could prevent a tumour from developing resistance to treatment.

Professor Young added: "Our research has allowed us to find out what switches are targeted by different drugs so that we can learn to mix and match far more effectively than is currently possible."

One cell-death molecule which triggers a number of suicide switches is called CD95L. Professor Young inserted this into a virus which was used to infect drug-resistant cancer cells. It effectively short circuited the cells' jammed suicide switches, knocking them into suicide mode even though some of them had not been flicked.

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