Cancer Research Campaign: Grounds for hope: treatments to come

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ADEPT

- antibody-directed enzyme prodrug therapy - is a two stage therapy. The patient is given an injection containing millions of antibodies each of which has a specific enzyme, unique to the body, fixed on its back. The antibody binds on to cancer cells, taking the enzyme with it. Two days later the patient is injected with the toxic cancer drug, the prodrug, but it is activated only by the enzyme already on the cancer cells, destroying the cancer within minutes, but leaving healthy cells alone. Scientists have been working on it for 11 years and clinical studies on bowel cancer patients have just started at the Royal Free Hospital, London.

GDEPT

GDEPT - gene-directed enzyme prodrug therapy - is one of a raft of gene therapy tehcniques being studied. Here the enzyme is transferred directly into the cells. Research is at an early stage.

P53 tumour suppressor genes

The p53 protein, the "guardian angel gene" protects the body against the proliferation of fast-multiplying cancer cells by instructing them to "commit suicide" and acts as a natural brake on the spread of cancer.

In about 60 per cent of all cancers, p53 is either absent or defective, so allowing cancer cells to replicate unchecked. The gene was discovered 19 years ago by Professor David Lane, now heading a CRC programme of molecular oncolcogy at Dundee University. Various ways of correcting the p53 gene are being looked at including importing a new pristine p53 into the damaged cells, perhaps by using the common cold virus to piggy back it into the cancer cells.

A test for damaged p53 genes could be available in five year's time.

Temozolomide

People with glioma - the most common brain cancer - die unless the tumour can be surgically removed. Unlike most brain cancer drugs, Temozolomide can get across the blood-brain barrier, it can be taken by mouth and the side-effects are not severe. It is hoped it will be available next year under the name of Temodal.

Vascular targeting (Angiogenisis inhibitors)

These work by cutting the blood supply to the tumour. In order to grow beyond the size of a small pea, tumour cells need to acquire a blood supply and these blood vessels grow into the tumour rapidly and chaotically. Drugs such as Combretastatin A4 have had remarkable success in acting on the blood vessels, causing vascular shutdown, which means that the tumour shrinks. Laboratory tests show that Combretastatin could kill up to 95 per cent of solid tumour cells, leaving healthy cells untouched.

Antisense drugs

Another type of genetic drug which targets gene defects in cancerous cells, rather than killing cells wholesale. Our genes hold DNA, the genetic blueprint, and RNA, the copy. In some cancers, the RNA instructions are faulty and the cell becomes cancerous. The idea is to correct the faulty instruction before the cell "reads" it. The Cancer Research Campaign is funding research into antisense targeting of mutations of the Ki-ras gene, implicated in four out of 10 cases of bowel cancer.

New treatments developed by the Cancer Research Campaign would never reach the patient without technology transfer. This is done in the UK by Cancer Research Campaign Technology, which patents discoveries, licenses them to industry and returns profits to the Campaign.

- Barbara Rowlands

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