|
Prostate disease and the pharmaceutical industry
Prostate Cancer
Possible future directions
Discovering and developing a new medicine is a process that
takes a long time. Unfortunately, many early successes in
finding new treatments later prove to be blind alleys. It
takes many years before a promising new compound can eventually
be used in the wider population.
Antiandrogens and 5-alpha reductase inhibitors are currently
being studied in combination. This should block testosterone
receptors without causing testosterone levels to fall too
far, thus reducing the risk of impotence and loss of interest
in sex.
As cancers grow, they have to develop their own blood vessels
– a process called angiogenesis. Medicines that can prevent
angiogenesis could stop tumours growing by depriving them
of oxygen and nutrients. This is a very active area of research;
a compound derived from the African bush willow that works
in this way is combretastatin A4. Discovered by scientists
at the Cancer Research Campaign, it is being developed in
association with the biotech company OXiGENE. Small-scale
studies in several cancer centres showed that blood flow to
tumours was significantly reduced when patients were given
weekly doses. Large-scale trials are due to begin shortly.
A related compound called AC-7700 (Ajinomoto) also blocks
angiogenesis and appears to be active against advanced solid
tumours.
AstraZeneca also has two compounds which target the tumour
blood supply, ZD6126 and ZD6474, and both are due to begin
clinical trials in 2000, while Maigainin Pharma is investigating
an anti-angiogenic compound called squalamine found in the
dogfish shark. Safety studies in people are complete, but
trials in prostate cancer are only at the planning stage.
Meanwhile, Abbott is studying ABT-627, which binds to specific
receptors on blood vessel walls and may interfere with blood
vessel growth. Evidence of improvement in people with prostate
cancer has been obtained in double-blind placebo-controlled
studies in the USA. In the context of angiogenesis inhibitors,
a recent study has shown that the 5-alpha reductase inhibitor
used in BPH, finasteride (Merck, Sharp & Dohme), is able to
prevent the production in prostate cancer tissue of a factor
called VEGF that promotes angiogenesis. This might provide
a rationale for its use in prostate cancer prevention as well
as BPH.
Recent press reports suggest that aspirin may help prevent
prostate cancer or alter its course. One of the activities
of aspirin is to block an enzyme called COX-2 (cyclooxygenase-2),
whose levels are four times higher in prostate cancer cells
than in normal ones. Hence, several medicines that strongly
inhibit COX-2 which are already used in arthritic disease
are likely to be tested in clinical trials in prostate cancer
in 2001. Interestingly, Pierre Fabre’s lipidosterol extract,
a dual Type 1 and Type 2 inhibitor of 5-alpha reductase, also
blocks COX enzymes, implying that it too might have a role
in prostate cancer as well as BPH.
|
