On 23 December 1971, Richard Nixon signed the National Cancer Act. It poured federal money into cancer research and handed the public a phrase that has outlived everyone in the room: the war on cancer.
It was a good slogan. Wars have an enemy, a front line and, eventually, a victory. Twenty-five years later, the pharmacologist Michael Sporn took stock in The Lancet. There had been real triumphs, he wrote: cures for childhood leukaemia, Hodgkin's disease and testicular cancer. But the flood of new molecular biology had barely moved the death rates for the common cancers that kill most adults.1 More than fifty years on, people still ask the question the slogan invites. If this is a war, why haven't we won it?
I think the question is wrong, because the metaphor is wrong. Cancer is not an invader. It is us.
An enemy made of your own cells
Every cancer starts with a single cell in your own body. Over years, that cell picks up mutations, from copying errors, from chemicals, from radiation, from its own faulty repair machinery. Most mutations do nothing. Occasionally one lets the cell divide a little faster, or ignore a signal to stop. Its descendants outgrow their neighbours. One of them picks up another useful mutation, and the process repeats.
This is evolution by natural selection, happening inside a single person.2 The cells that win are the ones best at surviving in the body, not the ones best for the body. Along the way they often lose the ability to mature into the specialised cells they were meant to become, which is why disrupted differentiation is now listed among the core traits of cancer.3
Sequencing has shown how few steps this takes. Across thousands of tumours, researchers have found about 140 genes that can drive cancer when mutated. A typical tumour carries only two to eight of these driver mutations. The rest of its mutations are passengers along for the ride.4
The immune system is not blind to any of this. It catches and destroys many early tumours, and the ones that survive have often been shaped by that pressure, a process called immunoediting.5 Checkpoint inhibitors, one of the biggest advances of the past fifteen years, work by releasing the brakes tumours put on immune cells that can already see them.6
A different cancer in every corner
If cancer is evolution, then a tumour is not one enemy. It is a population, and populations diversify.
In 2012, Marco Gerlinger and colleagues in London took multiple biopsies from different regions of the same kidney tumours and sequenced each one. Between 63 and 69 percent of the mutations they found were not present in every region of the tumour.7 A single biopsy, the standard way to diagnose cancer, was sampling one branch of a family tree and missing the rest.
This is what makes cancer so hard to cure. It is not one disease, or even one disease per patient. It is a crowd of related cell lineages, each a little different, and a treatment that kills most of them leaves the survivors to regrow.
The closest thing to a victory
There is one story that comes close to the war on cancer working as advertised.
Chronic myeloid leukaemia is driven by a single genetic accident. Two chromosomes swap pieces, fusing a gene called BCR to one called ABL. The fused gene makes a protein that tells blood cells to keep dividing. The shortened chromosome is called the Philadelphia chromosome, after the city where it was first seen.
In the 1990s, Brian Druker and colleagues tested a small molecule designed to block that one protein. The results, published in 2001, were extraordinary. Of 54 patients who received a dose of 300 milligrams or more a day, 53 saw their blood counts return to normal, usually within four weeks.8 The drug, imatinib, sold as Gleevec, was approved in the United States that year. In Sweden, the life expectancy of people diagnosed with CML now approaches that of the general population.9
One target, one drug, one disease turned from fatal to manageable. If any cancer story deserves the war metaphor, it is this one.
But in the same year imatinib was approved, a team at UCLA reported patients whose leukaemia had come back while they were still taking it. The cancer cells had either mutated the target protein so the drug no longer fit or made extra copies of the gene to overwhelm it.10 Even against the simplest cancer we know, evolution found a way around.
Resistance like this, to chemotherapy and to targeted drugs alike, is one of the central problems in cancer research.11 Most cancers are not driven by one mutation. They are driven by several, in a population of cells that varies from region to region, and every treatment selects for whatever can survive it.
Managing evolution instead
If the war metaphor is wrong, what replaces it? I find it more useful to think of cancer the way we think of antibiotic resistance, or of farming a field full of weeds. You cannot win once and walk away. You prevent what you can, catch what you can early, and treat in ways that make it harder for the survivors to take over.
That framing also makes the progress easier to see. In the United States, cancer death rates have fallen steadily since 1991, averting an estimated 4.5 million deaths. The gains came from three places: fewer people smoking, earlier detection of some cancers, and better treatment.12 None of them was a single decisive battle. All of them were steady work against an opponent that keeps changing.
There will probably never be one cure for cancer, because there is no one cancer. But there are already many cures for particular cancers, and many more cancers that people now live with for decades. That is not losing a war. It is what winning looks like against evolution.