`Magic bullet' cancer drugs give fresh hope of sparing healthy cells

A new generation of "magic bullet" drugs used as anti-cancer agents are offering fresh hope that substances that help kill off cancer cells without damaging healthy tissues can be developed.

Delegates to the American Association meeting here also heard it may become possible to "regrow" damaged or lost human tissues. A decade ago researchers believed drugs that could seek out and destroy cancers would soon be introduced, but the optimism was not realised.

The search continued, however, and Prof Jonathan Sessler of the University of Texas, Austin, described promising results arising from two new agents. "This is an old story and a new story," he explained.

The substances are texaphyrins, originally developed 20 years ago. But new versions have been developed that find their way to a tumour site and then amplify the damaging effects delivered by radiation or infra-red light.

The key, Prof Sessler said, was in making the texaphyrin molecule bigger by adding an extra nitrogen complex. This meant that it could carry a heavier metal, which in turn seems to assist in doing greater damage to the cancer cells. One problem with the old magic bullet approach was that the substances would accumulate in tumours but also in healthy tissue and all were liable to be damaged.

These new compounds localise in tumour sites at rates 10 times higher than normal tissues, he said. "We don't quite know the answer" why they localise so well, he said. But they do not act on their own. The tumour site must be exposed to radiation or to infra-red light after the drug is given.

When struck by radiation the compound creates hydroxol radicals and if infra-red light is used, oxygen radicals are produced. These substances destroy the cancer cell but do little damage to surrounding healthy tissue.

The substances are still being tested but already treatment improvements have been noted in reducing secondary brain tumours. The typical survival period for such patients is only four months but treated patients' survival is about a year, he said, and could be longer as many patients continue to survive.

Equally exciting work is under way in tissue regeneration following the discovery of a genetically modified mouse that is able to regrow lost tissues. Mammals suffering injuries experience ordinary regrowth with wound healing and the production of scar tissues, explained Prof Ellen Heber-Katz of the Wistar Institute in Philadelphia.

Regeneration is much different and involves the full replacement of all tissues without scarring. Amphibians which lose a limb can regrow the full limb including all the different types of tissues from skin to nerves and bone. The mice involved have a modified immune system and are unable to produce certain types of T-cells which are part of the immune system. Their ability to regenerate was discovered when small punches, made in their ears for identification purposes, healed without a trace.

"The hallmark of regeneration as in amphibians is met in every case in the way these animals regenerate their wounds," she said. "We think that this could be a very good model for regeneration in mammals."

Limited experiments have already been undertaken to assess their potential for regeneration. A one-centimeter segment of tail was cut away and most of this grew back, including skin and fur. Ten per cent of another mouse's liver was removed and this too regrew back to normal size. Liver regeneration occurs in mammals but normal mice sectioned in this way did not regrow liver as quickly and it took much longer before appropriate liver volume was restored.

Work is already under way to identify how the absence of certain T-cells allows the tissues to replace themselves. Amphibians have a different immune system and are able to produce a growth of undifferentiated cells which then grow into the various tissue types found in a complete limb. The thinking is that mammals as they evolved traded off regeneration in favour of having a much more powerful immune system.

T-cells normally have a role in attacking and destroying cells which they would recognise as "abnormal", including any undifferentiated cells. Their absence in the mice may allow undifferentiated cells to survive and then replace the missing tissues.