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FOR men with advanced prostate cancer, the outlook is usually bleak. A drug
called doxorubicin can kill the tumour cells, but the doses needed are so high
they are likely to kill the patient too. Now researchers at Merck Research
Laboratories in Pennsylvania have found a way to target the drug at the
cancer.

The team took advantage of an enzyme called prostate-specific antigen (PSA),
which is only present at noticeable levels in the prostate鈥攖he small gland
in men that produces seminal fluid. PSA splits the gel-like proteins in semen,
making it runny enough to ejaculate. In men with prostate cancer, the
PSA-secreting cancer cells multiply, increasing the amount of PSA.

Conventional doxorubicin is harmful to cells throughout the body. So the
researchers attached the drug to peptide molecules, which prevent it from
entering cells and doing any damage. 鈥淥ur compound is much less toxic, so we can
give ten times more of it,鈥� says Raymond Jones, who led the Merck team. Jones
and his team reasoned that when the drug reached the prostate, PSA would split
the peptide, making the drug molecules small enough to enter cancer cells and
kill them.

They tested their drug, called L-377202, on mice that had received
transplants of human prostate cancer cells (Nature Medicine, vol 6, p
1248). Conventional doxorubicin used at its maximum permitted dose reduced the
tumour by 5 per cent, while L-377202 killed off 90 per cent of the cancer
tissue. With preliminary tests on patients almost complete, Jones says he is
鈥渃autiously optimistic鈥�.

Prostate cancer expert David Dearnaley of the Institute of Cancer Research
said: 鈥淚t is a very exciting development.鈥�