My latest Mind and Matter column in the Wall
Street Journal is on cancer and evolution by natural selection:
Last week the American Cancer Society reported that death rates
from cancer are falling steadily, at an annual rate of about 1.9%
in men and 1.5% in women. A study published this week by the
University of Colorado found that most seniors who died after being
diagnosed with breast cancer actually lived long enough to have
died of something else.
Prevention explains much of the decline in cancer fatalities,
especially the drop in smoking. As for treatment, the most
promising new options harness the very force that makes cancer so
stubbornly virulent in the first place: evolution.
Adjusted for age, the incidence of some cancers has also been
falling, contradicting the expectation widespread in the 1960s and
1970s that cancer rates would surge because of chemical pollution
and the use of pesticides. In thrall to this view, Wilhelm Hueper,
the mentor of Rachel Carson, refused to accept that lung cancer was
caused by smoking. He said the data "unmistakingly suggest that
cigarette smoking is not a major factor in the causation of lung
cancer" and "it would be most unwise at this time to base future
preventive measures of lung-cancer hazards mainly on the cigarette
theory."
Better treatments have played at least some role in the cancer
death rate's recent improvement. Surgery, radiation therapy and
chemotherapy save or prolong many lives, though they're often very
blunt instruments that kill tumors only slightly faster than they
kill patients.
A new generation of more effective and less vicious treatments
is starting to make a difference, too. Imatinib (marketed as
Gleevec), the first therapy that targets a specific enzyme
expressed by cancer cells-rather than just kill cells that are
dividing, like most chemotherapy-has now been saving lives for 10
years and is approved for 10 kinds of cancer. Others, such as
vemurafenib for melanoma, are joining in.
Yet, by comparison with the rapid progress in rich countries
against death from infectious disease, respiratory disease, heart
disease and stroke, success against cancer is still far too slow
and attritional. The chief reason for this is evolution. Because a
tumor consists of a bunch of cells competing for the body's
resources by growing and dividing, and because it indulges in
massive genetic trial and error, it experiences extremely rapid
natural selection. Throw a drug at a tumor and you selectively
benefit those of its cells that happen to be the most resistant to
the drug. That is why most cancer treatments start out so well and
then gradually lose the battle.
Logically, therefore, medicine needs to harness evolution to its
cause, too. The "organ" that exploits natural selection most
effectively is the immune system, which uses trial and error to
find suitable antibodies to counter infectious diseases. So the
growth of immunotherapy for cancer seems to be a promising angle,
especially in the form of therapeutic cancer vaccines.
Dendreon's Provenge is the first to be approved, for advanced
prostate cancer. The physician extracts cells from each patient's
own immune system, selectively "trains" them to attack
prostate-cancer cells, then multiplies them and reintroduces them
into the body. The "training" is, in effect, a form of evolution by
natural selection, in which the cells multiply if they can attack
an antigen specific to prostate cancers. Provenge gives patients a
50% greater chance of being alive after three years.
This year, a large-scale clinical trial begins for Prima
BioMed's CVac, which takes a similar approach to ovarian cancer.
Cells from the patient's blood are matured into dendritic cells.
Those dendritic cells that can train killer cells to go after
mucin-1, a protein on the surface of ovarian cancer cells, are
selected and then reintroduced under the patient's skin.
Cancer vaccines are not magic bullets, and many have failed in
clinical trials after promising early results. But their most
hopeful feature is that they are beginning to use cancer's greatest
defense-evolution by trial and error-against it.
