We Fought Cancer…And Cancer Won.

In response to the limits of targeted therapies, scientists are pursuing the next big idea: that there is no such thing as cancer. There are only cancers, plural, each one characterized by a different set of mutations, a different arsenal it uses to fight off drugs and proliferate. "By the time there are 10 cancer cells, you probably have eight different cancers," says Demetri. "There are different pathways in each of the cells." And that's why cancer patients keep dying. One woman found a lump in her breast in 2002, nine months after a mammogram had shown nothing amiss. She had the breast tumor removed, says oncologist Julie Gralow, who treated her at the Fred Hutchinson Cancer Center, and chemotherapy to kill any remaining malignant cells. The woman did well for three years, but in 2005 an exam found cancer in her bones. She underwent half a dozen different chemotherapies over the next three years, until last March the cancer was detected in her brain. She received radiation—because chemo drugs generally do not cross the blood-brain barrier, radiation rather than chemo is the treatment of choice for brain cancer—but by July tumors had riddled her body. She died that month.

To beat down cancer mortality, oncologists need to target all the many cancers that make up a cancer—the dozens of different pathways that cells use to proliferate and spread. That is the leading edge of research today, determining how this patient's tumor cells work and hitting those pathways with multiple drugs, simultaneously or sequentially, each chosen because it targets one of those growth, replication and angiogenesis pathways. "The hope is to match tumor type to drug," says Roy Herbst. "We need to make the next leap, getting the right drug to the right patient."

Both presidential candidates have vowed to support cancer research, which makes this a propitious time to consider the missed opportunities of the first 37 years of the war on cancer. Surely the greatest is prevention. Nixon never used the word; he exhorted scientists only to find a cure. Partly as a result, the huge majority of funding for cancer has gone into the search for ways to eradicate malignant cells rather than to keep normal cells from becoming malignant in the first place. "The funding people are interested in the magic-bullet research because that's what brings the dollars in," says oncologist Anthony Back, of the Hutch. "It's not as sexy to look at whether broccoli sprouts prevent colon cancer. A reviewer looks at that and asks, 'How would you ever get that to work?' " And besides, broccoli can't be patented, so without the potential payoff of a billion-dollar drug there is less incentive to discover how cancer can be prevented.

Another missed opportunity involves the environment around a tumor cell. "We used to focus on cancer cells with the idea that they were master of their own destiny," says MIT's Weinberg. "By studying genes inside the cell we thought we could understand what was going on. But now [we know] that many tumors are governed by the signals they receive from outside"—from inflammatory cells, cells of the immune system and others. "It's the interaction of signals inside and outside the tumor that creates aggressiveness and metastasis."

Which leads to the third big missed opportunity, the use of natural compounds and nondrug interventions such as stress reduction to keep the microenvironment inhospitable to cancer. (Cancer cells have receptors that grab stress hormones out of the bloodstream and use them to increase angiogenesis.) "Funding has gone to easier areas to research, like whether a drug can prevent cancer recurrence," says Lorenzo Cohen, who runs the integrative care center at M. D. Anderson. That's simpler to study, he points out, than whether a complicated mix of diet, exercise and stress reduction techniques can keep the micro-environment hostile to cancer. And while we're on the subject of how to reduce mortality from cancer, consider these numbers: 7 percent of black women with breast cancer get no treatment, 35 percent do not receive radiation after mastectomy (the standard of care), and 26 percent of white women do not. As long as scientists are discovering how to thwart cancer, it might make sense to get the advances into the real world.

Breakthroughs continue to pour out of labs, of course. Cutting-edge techniques are allowing scientists to identify promising experimental drugs more quickly than ever before. And just last week separate groups of scientists announced that they had identified dozens of genes involved in glioblastoma, the most common brain cancer, as well as pancreatic cancer. That raises the possibility that the mutations cause the cancer, and that if the pathways they control can be blocked the cancer can be beaten back. Stop us if you've heard that before. Hope springs eternal that such findings will not join the long list of those that are interesting but irrelevant to patients.

With Anne Underwood and Jeneen Interlandi in New York and Mary Carmichael in Boston

© 2008