Monday, February 28, 2011

Emperor of all maladies

Physicians of the Utmost Fame
Were called at once, but when they came
They answered, as they took their Fees
“There is no Cure for this Disease.”
                                         --Hilaire Belloc
In the last chapter of his book “The Emperor of All Maladies,” cancer researcher Siddhartha Mukherjee asks the question: Are we winning or losing the War on Cancer? It’s a question that’s been asked repeatedly over the last 40 years, and for good reason: whatever progress has been made in this effort is not conspicuous to those who have the most skin in the game.

That, of course, would include people like me.

What constitutes progress in cancer research is meager by any measure—even if you’re totally sold on its importance as a national investment. The age-adjusted percentage of Americans dying from cancer is about the same now as it was when President Nixon declared war on cancer in his State of the Union address in 1971. Meanwhile, death rates for heart disease and stroke have been slashed by 59% and 69% during the same time. Cancer remains relentless and insidious.

Where there have been survival gains for the more common forms of cancer, these are measured in additional months of life, not years. The few dramatic increases in cure rates and patient longevity have come in a handful of less common malignancies, including Hodgkin’s, some leukemias, thyroid and testicular cancer, and many childhood cancers.

Most of the modest gains we’ve seen cannot be credited to the drugs discovered by the NCI or the big cancer research centers—where nearly all of our public money goes. Instead, we’ve gotten better at catching more tumors earlier (think mammography) and at convincing people to quit smoking. Education and prevention is where an investment of money appears to be paying off. Tragically, the $200 billion or so that’s been channeled into R&D for new cancer drugs since 1971 has barely dented cancer survival statistics.

Most people I talk to about this subject resist such a negative conclusion or express surprise over it. Many of us know someone who is alive today because they received what seemed like a miracle drug. Those are the hopeful, but uncommon stories that stick with us, and which fundraisers use to great effect in their campaigns. There is a disconnect, however, between what we want to believe to be true about progress in the war on cancer, and where we actually stand. We want to believe there is a cure for any form of cancer that might befall us.

Among those who are actually engaged in medical research, the great majority are optimistic about the progress we’re making. They believe we’re gaining knowledge that will someday lead to viable treatments for the 100-plus diseases we group as cancer. Most feel we’re on the right path. Some recklessly claim that cures are right around the corner.

Mukherjee would not count himself among that group. He pleads that the war on cancer may best be “won” by redefining victory.

“With cancer, no simple, universal or definitive cure is in sight—and is never likely to be,” he wrote. “To keep pace with this malady, you need to keep inventing and reinventing, learning and unlearning strategies.” His book, a “biography of cancer,” is a testament to the human ingenuity, but also the hubris, that has defined the search for understanding the disease.

The challenge with finding effective treatments is embedded in the biology of cancer. At its simplest, this disease is a flaw in how our cells divide. Genetic mutations occur when DNA is damaged by carcinogens (like ultraviolet light), but also by seemingly random errors in copying genes when they divide. Conceptually, the battle against cancer pushes the idea of medical treatment to its limit, for the object being intervened upon is our genome—the hereditary information that makes us who we are.

Mukherjee states that it’s unclear whether an intervention that discriminates between malignant and normal growth is even possible.

“Perhaps cancer, the scrappy, fecund, invasive, adaptable twin to our own scrappy, fecund, invasive, adaptable cells and genes, is impossible to disconnect from our bodies. Perhaps cancer defines the inherent outer limit of our survival.”

A more reasonable goal than seeking cures, he argues, may be to simply play along with cancer’s cat-and-mouse game for the foreseeable future. If the grim game of treatment, resistance, recurrence and more treatment can be stretched out longer and longer through various forms of therapy, then it will transform how we think about this ancient illness. It’s possible that some forms of cancer could be turned into chronic diseases, much as we’ve done with AIDS.

Because of research, we have gained an extraordinary glimpse into the biology of cancer. The complete maps of mutations in many tumor types will soon be complete, just as the Human Genome Project was painstakingly mapped a decade ago. But as the Haitian proverb tells us, there are mountains beyond mountains. Once scientists discover what the mutant genes are, they will need to understand what the mutant genes do. Anyone who expects cancer to quickly yield to sophisticated science hasn’t been paying attention to what history has already taught us about the disease. It's been said that one tumor is smarter than a hundred scientists.

Is the War on Cancer being won or lost? At what seems an unacceptably high cost and over a longer time scale than seems reasonable, I would say the war has advanced intermittently and inconsistently. The “easy” cancers have partially yielded to human genius and have become manageable diseases. But Mukherjee reminds us that cancer is indeed built into our genome and is what he calls “the leaden counterweight to our aspirations for immortality.” Another way of putting this is that our bodies are made to eventually die. Cancer may be simply be the mechanism to assure that they do.

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