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.
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