We grossly underestimated the cleverness of cancer"

Medical science has made incredible advances in our lifetimes — but one sobering truth remains. "If you look at the death rate from cancer, there's no dramatic change over the last five decades," says David Agus, author of The End of Illness and the head of University of Southern California's Westside Cancer Center. "There are little wins, but no dramatic change."

On the plus side, the incidence rate of cancer has gone down somewhat, as fewer people smoke and some obvious carcinogens have been eliminated from the environment.

It's true that we've learned a lot more about cancer in the past 50 years — but mostly what we've learned is that cancer is a lot more complicated than we thought.

"We truly grossly underestimated the cleverness of cancer," says Ralph deVere White, director of the U.C. Davis Cancer Center. We're sequencing the genomes of many cancers, and what you discover is that "regrettably, they have many more molecular changes than we ever saw."

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Dr. White adds that we've learned more about cancer in the past 10 years than we had learned in the previous 2000 years. "Cancer never allowed us to get so much information to address our inadequacy." And now, the challenge is to "turn that data into knowledge," which requires a lot of cutting-edge bioinformatics. (Too bad everybody's funding is being cut right now, at a crucial time in cancer research.) Melanoma image via National Cancer Institute.

You probably already know that cancer is not just one disease — it's many diseases, gathered under a single umbrella. But in the past, we thought there were types of cancer called "breast cancer" or "prostate cancer," which were basically site specific — and now we've found that cancer is much more varied.

"Cancer is hundreds if not thousands of different diseases," says David Weinstock, an assistant professor with the Dana-Farber Cancer Institute and Harvard Medical School. "Saying, 'Why don't we have a cure to cancer,' is like saying, 'Why don't we have a cure to infection.'"

There are multiple levels of complexity, adds Weinstock: You have different basic types, like colon cancer versus lymphoma. Then you have hundreds of different types of lymphomas, and then every single person's lymphoma is different at a molecular level. And even though you think of cancer cells as all identical, in fact "not every cancer is the same, [and] there are many differences within a tumor." When you attack a tumor, "you're killing a diverse population" of cells, some of which will be resistant.

Most cancers under treatment have 100 different mutations within a single tumor, says Agus. "It's very hard to model that."

Meanwhile, you have to kill the tumor without killing the person who has it. People talk about the "therapeutic index," says Weinstock — which is the chances of killing the tumor, versus the chances of killing a normal cell.

Another wrinkle: cancer cells are bi-directional, meaning that stem cells can differentiate into mature tumor cells — but mature tumor cells can also turn back into stem cells, says Agus. Thus, treatments that have involved just killing the stem cells in the hopes that this would keep the cancer from recurring have failed, because the tumor can always repopulate with more stem cells.