MOST
cancers are equal-opportunity killers. Some, though, are perforce
sex-specific. Breast cancer is rare in men. And prostate cancer is
obviously absent from women. Recent
years have seen a plethora of new
drugs-starting in 1998 with Herceptin-for treating breast tumours that
are threatening to get out of control. No such breakthrough
has happened with prostate cancer. Though easily treated if caught
early, late-stage prostate cancer is serious and often fatal. But that
may be about to change.
Better
understanding of the biology of the disease, and particularly of the
role of testosterone in promoting it, has stimulated a new era of drug
development, reminiscent of the revolution that ushered in Herceptin.
These novel treatments, which are now undergoing clinical trials, were
one of the main topics of conversation at the Congress of the European
Association of Urology, which took place in Paris on February 24th-28th.
In this section "The men's room, the wow factor, Violating the rules Smarter than the average bear.
Some
of the therapies discussed remain conceptual almost to the point of
fantasy: a genetically engineered virus that could destroy
prostate-cancer cells from within, for example. Several, though, are
already available, or are just about to be.
Cabazitaxel,
made by Sanofi, a French firm, is one. It is a relative of taxol, a
drug used to treat breast and ovarian cancer. It works by preventing the
formation of structures called microtubules, which pull the chromosomes
apart in dividing cells (such as cancer cells). It was approved for use
in 2010 after trials showed that it could prolong the lives of men with
late-stage disease. A second drug, abiraterone, made by Johnson &
Johnson, an American company, was approved in 2011 after a trial was
stopped because it had been so successful that the organisers deemed it
unfair on those in the control group that they were not receiving the
medicine too.
Abiraterone
works by interfering with an enzyme involved in the production of
testosterone. Crucially, it does so in all testosterone-producing
tissues, particularly including the adrenal glands, not just the testes.
A common change that occurs when prostate cells turn cancerous is that
they become extremely sensitive to testosterone-so much so that
late-stage prostate cancer is often referred to as being
"castration-resistant", because even that drastic testosterone-reducing
treatment cannot halt it. But abiraterone can.
Testosterone poisoning
Cutting
off the testosterone supply is not, however, the only approach
possible. MDV3100, made by Astellas, a Japanese firm, and Medivation, an
American one, reduces the cancer's sensitivity to what testosterone is
already there. This drug, not yet approved for prescription, works by
gumming up testosterone receptors on the cancer cells' surfaces, so they
cannot react to the hormone. It also cuts the lines of communication
between any receptors which are still activated and the cell nucleus, so
that the nucleus cannot take instructions from the hormone.
A
fourth drug, alpharadin, developed by Algeta, a Norwegian firm, has a
completely different mechanism of action. It works not on the primary
cancer but on one of its most dangerous consequences, secondary bone
tumours. Ironically, its active ingredient is radium, a substance more
usually thought of as a cause of cancer than as a treatment. But one
reason radium is dangerous is that, as a glance at the periodic table
will show, it is chemically similar to calcium, a principal ingredient
of bone. It therefore gets absorbed by bones if ingested, rather than
being excreted.
Algeta's
researchers have exploited this to produce a drug that is taken up by
bones. In someone who already has cancer that is a good thing, because
the radiation produced kills the cancer cells, and the drug gets
concentrated where it is needed most.
It
sounds desperate, and it is. But it seems to work. A trial at the Royal
Marsden Hospital, in London, was stopped last year for the same reasons
that the abiraterone trial was stopped: the treatment was too successful
to deny it to the control group. Alpharadin is now, therefore, awaiting
approval by the authorities.
The
final proven approach to castration-resistant prostate cancer is a
vaccine. This is not a prevention, in the way that most vaccines are,
but a treatment for existing disease. Sipuleucel-T, as the vaccine in
question is known, is made by Dendreon, an American firm. The starting
point is a culture of human dendritic cells. These are part of the
immune system and, if suitably treated with a substance called a fusion
protein, can be used to make prostate-cancer cells vulnerable to immune
attack.
Sipuleucel-T's
main drawback is that each treatment has to be handcrafted to the
individual receiving it, using dendritic cells from his own body. This
is hugely expensive-almost $100,000 a course. That is a sum which
insurance companies and government health services might understandably
be reluctant to fork out.
Cost,
indeed, is a consideration for others among the new
anti-prostate-cancer treatments. Britain's National Institute for Health
and Clinical Excellence, which assesses the cost-effectiveness of new
medicines that might be paid for by the country's National Health
Service, reckons, for example, that abiraterone is too expensive to
justify the extra months of life it brings. But Herceptin, too, was
subject to scrutiny about its cost at the beginning. Now Herceptin
treatment is routine, and many women's lives are the better (and longer)
for it. With luck, in a few years' time, men will be able to say the
same.
Culled- The Nation
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Prostate cancer is very bad disease for human life. Prostate cancer occurs when cells in the prostate gland grow out of control. There are often no early prostate cancer symptoms, but some men have urinary symptoms and discomfort.
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