Pervasive, elusive and tough, cancer has proved to be a formidable foe against generations of bright and well-funded researchers.

Although there was never an official declaration, military rhetoric became the cliché among journalists covering cancer research as President Nixon signed the U.S. National Cancer Act in December 1971. The "reconnaissance" might be completed in labs and "offensives" inside the body, but like the war on drugs and the war on terror, trying to root out this disease has been more difficult and more expensive than originally hoped.

In the past 40 years, the National Cancer Institute has spent some $90 billion on research and treatment. And national estimates peg the annual price tag of cancer care at about $125 billion in 2010, noted reporter David Malakoff in a special section of Science's March 25 issue, commemorating the 1971 bill's signing.

Contributing to this ever-growing tab are a combination of larger patient pools and pricier drugs. Although they are the minority, some individual therapies can cost tens of thousands of dollars and bring less than an extra year of survival. And as more people live longer after their initial diagnosis, the costs of treatment are projected to keep climbing. By 2020, treating the most common forms of cancer is likely to increase 27 percent to some $157.7 billion—regardless of whether the price of treatment itself increases—according to a January report in the Journal of the National Cancer Institute.

And like the attack on other nebulous, if more macro-scale enemies such as drug cartels and terrorist cells, cancer is a slippery and diverse entity. More than 100 forms of the disease are currently recognized, making it nearly impossible to create uniform models or stats. Within those many categories, individual cases present with innumerable variables, driving interest in personalized therapies, such as Provenge, which was approved by the FDA in 2010.

This direction is, however, often at odds with current policy pushes to assess larger populations of patients to find trends in effectiveness. And the doctors in charge of charting treatment strategies struggle to apply large data sets—when they are available—to individual patients, for whom they more often than not are prescribing cancer drugs for purposes other than those for which they have been approved, a practice known as off-label use.

Even within a single patient, "the population of cells in a tumor is quite heterogeneous, making it very unlikely that any single therapy can target them all," Science editor-in-chief, Bruce Alberts writes in the new issue. And "by the time most cancers are detected, a tumor has grown to contain more than a billion cells. Through a process resembling mutation and natural selection stretching over many years, these cells have become altered in ways that allow them to escape from the large number of failsafe mechanisms that normally protect the human body."

Meanwhile, researchers are still sorting out the basic biology of cancer development, such as how it spreads into other organs of the body, a process called metastasis. As Christine Chaffer and Robert Weinberg, both of the Whitehead Institute for Biomedical Research and Massachusetts Institute for Technology, note in their paper in Science, "Metastasis causes the most cancer deaths, yet this process remains one of the most enigmatic aspects of the disease."

As cancer's core has proved almost impenetrably complex over the past decades, study of the disease has been spreading rapidly into new disciplines, such as genetics, genomics and immunology. The immune system plays key roles in warding off cancer, Robert Schreiber, of the Washington University School of Medicine, Lloyd Old, of the Memorial Sloan-Kettering Cancer Center, and Mark Smyth, of the Peter MacCallum Cancer Center in Australia, wrote in their paper in the new issue of Science. "The immune system controls not only tumor quantity but also tumor quality."

Since the U.S. boosted its funding to beat back cancer 40 years ago, mortality rates are in decline, falling 21 percent for men and about 12 percent for women between 1991 and 2006, according to the American Cancer Society. More than 1.5 million new cancer cases were expected in 2010, which is up from the more than 1.3 million anticipated new cases in 2005, the group estimated.

And the disease has made serious inroads into other countries that have far fewer resources to manage it. In places where even general practitioners are few and far between, such as Rwanda, well-equipped oncologists are practically an anomaly, writes journalist Martin Enserink this week in Science. In some of the world's poorest countries about nine in 10 children diagnosed with leukemia will die from the disease, whereas in Western Europe survival is about 85 percent, he reports.

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