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'Double suicide gene' therapy may offer safer treatment for prostate cancer

ECCO-the European CanCer Organisation

A team of US scientists has become one of the first in the world to use a novel form of double "suicide gene" therapy to treat prostate cancer - and it's done so with the help of a common cold virus.

The injected adenovirus is used as a vector (transporter) to carry pairs of fused suicide genes directly into the cancer cells. This is followed by administration of two so called "pro-drugs", resulting in the secretion within the cancer cells of a toxic substance - which compels them to commit suicide.

The technique might sound simple, but exploiting the source of one of mankind's most common afflictions to attack one of its biggest killers highlights a major technological triumph. One of the big problems in gene therapy is getting the genetic material to the target. It is smaller than microscopic and notoriously hard to manipulate. Selecting an appropriate vector is critical.

Carried out by Professor Jae Ho Kim and colleagues at the Henry Ford Hospital, in Detroit, the new technique was developed in the hope that it would achieve "greater levels of targeted cytotoxicity" than single suicide gene therapy.

After carrying out a trial of 12 patients, all with recurring disease, Professor Kim believes that the technique may point the way forward to safer and more effective treatment. Current treatment options, including prostate removal and radiotherapy, are frequently associated with impotence and urinary incontinence.

Professor Kim told ECCO 11- the European Cancer Conference in Lisbon: "All patients tolerated the gene therapy well with minimal toxicities".

Half of the group showed varying degrees of therapeutic response for periods ranging from three weeks to a year and the team is now planning a further study incorporating radiotherapy.

Professor Kim explained: "Our 'trimodality' approach, i.e. viral, suicide gene therapy and radiotherapy, would potentially achieve a higher rate of tumor control without damaging critical normal tissue and organs".

The two "suicide genes" injected directly into the cancer cells in the preliminary study were the HSV1 derived (thymidine kinase gene and the E.Coli derived CD (cytosine deaminase) gene. The patients then received a week-long course of two drugs: ganciclovir and 5-fluorocystosine.

The study is one of several cancer programmes in the US involving common cold virus. The US National Institute of Health has approved about 20 gene therapy programmes in a major drive against prostate cancer, the most frequently diagnosed malignancy in American men.

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Abstract No. 580

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