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Folkman's insight was to look for substances that prevent tumors from building those pipelines. This approach worked beautifully in mice. Now more than 50 angiogenesis inhibitors are being studied in humans with a wide range of cancers; a dozen are in the final stages of testing. Thus far, only a tiny number of human patients treated with these compounds have seen their tumors shrink or disappear. Clinicians are nonetheless encouraged; while angiogenesis inhibitors don't make cancer go away, they do appear to slow tumor growth. And that means they may work best in conjunction with some of the other new treatments to batter cancer from several directions at once.
"We've seen results in very few patients yet," says Folkman. "But we have seem some patients with stable disease. We have seen some patients whose tumors have stopped growing. And we have seen some patients whose tumors slowly regressed. I think the approach is promising, but we are still learning."
While many scientists focus their attention on potential weaknesses in the cancer cell, others are concentrating on the flip side--recruiting the body's immune system to seek and destroy the renegade tissues. So far, this approach has proved less successful, largely because no matter how badly they are misbehaving, tumor cells are purely homegrown and thus presumed innocent by the immune system. When it finally catches on that something is wrong, it's usually too late.
That problem may not be insurmountable, as scientists at last week's clinical-oncology meeting made clear. The trick, it turns out, may be to put aside 99% of the immune system and focus on dendritic cells, a tiny but especially sensitive population of white blood cells that act as sentries to warn against invaders of all kinds. Scientists at California-based Cell Genesys, for example, have taken tumor cells from a number of cancers, genetically engineered them to pump out a hormone that stimulates production of a host of immune cells, and vaccinated late-stage lung-cancer patients with the mixture to boost chances that dendritic cells would sound the alarm against the tumors. In the latest study, three of 22 patients saw their tumors disappear completely, and four saw them stop growing.
Researchers at Stanford University have harvested dendritic cells from advanced-cancer patients, exposed the cells to potent growth factors, added tumor-specific proteins to sensitize them and reintroduced the mixture into patients as a vaccine. Of 12 patients with advanced colorectal and lung cancer, two watched their tumors shrivel away, and another is still tumor free a year after receiving the vaccine.
Whether you're talking about conventional therapy or one of these promising new approaches, experts agree the earlier you catch a cancer, the better your chances of controlling it. And thanks to a growing understanding of the cancer cell's natural life cycle, doctors are learning how to detect the disease at its very earliest stages. One well-known example is the prostate-specific antigen (PSA) test, which identifies a protein secreted by abnormally growing prostate cells before any symptoms appear. (The test is not perfect, however, since psa is also secreted, albeit in smaller amounts, by benignly growing prostate cells.)