BREAST cancer has a new enemy in the shape of combinations of genes that
persuade tumour cells to commit suicide, leaving healthy cells untouched. If
this kind of gene therapy is effective, it could be used to destroy other types
of cancer, too.
Nicholas Lemoine and his colleagues at Hammersmith Hospital, London,
announced their new approach at a British Endocrine Societies meeting in
Birmingham this week. Their technique exploits changes that make tumour cells
different from healthy counterparts. They inject 鈥渟uicide genes鈥� that are turned
on only in cancer cells. The genes code for enzymes that convert harmless drugs
into toxic compounds that kill tumour cells.
Genes are preceded by 鈥減romoters鈥�, sequences of DNA that that cells use to
switch genes on and off. One gene, called erbB2, is important in fetal
development, but is normally inactive in adult cells. But in 20 per cent of
breast cancers, the cells start making erbB2 again. So the researchers
attached the promoter sequence of the erbB2 gene to the suicide genes.
Unlike healthy cells, tumour cells recognise the erbB2 promoter, and go
on to make the enzymes that kills them.
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The researchers proved that the technique was safe in a recent clinical trial
in which they injected DNA containing a suicide gene into tumours in 12 breast
cancer patients. As they hoped, the gene was switched on only in cancerous
cells. 鈥淭hey are the first group to complete successfully a trial into gene
therapy for breast cancer,鈥� says Adrian Harris of John Radcliffe Hospital in
Oxford.
Now that Lemoine鈥檚 team has shown the technique affects only cancer cells, it
is trying out combinations of suicide genes. The idea is to maximise the killing
effect while reducing resistance to the therapy.
Suicide genes being tested include one that converts paracetamol into a toxic
chemical and another that turns a precursor into deadly cyanide. The researchers
are also trying to target different types of tumour by using different
promoters.
鈥淵ou could use different combinations for each particular type of cancer,鈥�
says Georges Vassaux, a member of the team. And genetic profiling could even
allow therapies to be tailored to individuals.
According to Harris, this mix and match approach is quite new. 鈥淣obody has
done combination gene therapy before,鈥� he says. But gene therapy will only work
if it treats cancer wherever it is in the body. The researchers plan to use an
adenovirus that will be injected into the blood and carry its cargo of genes
throughout the body. Tests on human cells grown in culture have been successful.
鈥淲e can kill 100 per cent of the tumour cells with no problem,鈥� says Vassaux.
Now they are testing the approach on mice before doing further clinical
trials.
Jo Reynolds of the Cancer Research Campaign says although such treatment is a
long way off, it鈥檚 an exciting approach. 鈥淵ou could use adenovirus for a
systemic therapy, but you need to have ways of targeting the genes to the tumour
cells. One of the wonderful things about gene therapy is that this will be
辫辞蝉蝉颈产濒别.鈥�
But she warns that there are concerns about the safety of using viruses for gene therapy
(see p 5).