This article was originally published by The Guardian to mark the centenary of World War 1 last year.
Few things evoke the horror of battle so powerfully as Wilfred Owen’s Dulce et Decorum Est.
“Gas! Gas! … flound’ring like a man in fire or lime … guttering, choking, drowning … blood come gargling from the froth-corrupted lungs.”
Mustard gas was originally used in the first world war, and even though it was subsequently outlawed under the Geneva Convention, over 2,000 nitrogen mustard bombs – 100 tonnes of the poison – were secretly stockpiled on a US ship anchored at Bari, an Italian base. When the SS John Harvey was blown up in a German air raid during the second world war, its secret cargo detonated, causing untold death and suffering – and sowing the seed from which cancer medicine would grow.
A chemical warfare expert arrived to confront the aftermath, and the postmortems he ordered showed something startling: people who had succumbed to the poison had very few lymph and bone marrow cells.
Back then, cancer was an enigma. One of the few things known was that cancer cells, like lymph and bone marrow cells, multiply much faster than normal cells. Following the principle that “the dose makes the poison”, scientists wondered if a low dose of nitrogen mustard could be used to treat cancer.
And so chemotherapy was born. Like war, it was dangerous and unpredictable, sometimes advancing, often forced to retreat. The first time a patient was treated with cyclophosphamide, the active part of nitrogen mustard, the tumour shrank – something not even thought possible at the time. But it was a temporary miracle. Treatment had to be stopped when the patient’s side effects became life-threatening in themselves.
Life starts as a single cell, and diseases, including cancer, start at the cellular level. Usually, disease-causing cells can be found and destroyed because they are obviously different from our normal, healthy cells. Penicillin attacks a part of bacterial cells that human cells don’t have, leading to the elimination of bacteria with no damage to us. But cancer is our own cells slightly altered, which makes it very challenging to treat.
For a long time, we thought our only chance was to attack rapidly dividing cells, and accept the collateral damage to normal cells that divide quickly: loss of healthy gut, immune system, hair – the devastating side-effects of aggressive chemotherapy. It was like waging war on Afghanistan to stop Bin Laden.
Thankfully, cancer medicine is going in a new direction. So, metaphorically speaking, we don’t go to war with an entire country to bring down one man. Instead we use intelligence (heightened knowledge of how cancer works) to track that man, then send in an elite team to stop him and only him (targeted therapy). The past few decades of research have revealed that many cancers have unique features that make them different from normal cells, and these differences provide us with cancer-specific drug targets.
One of these is a protein called HER2. About 25 out of 100 breast cancers have high levels of it on their cells, but the normal cells next to them have hardly any. In 1998, the US Food and Drug Administration (FDA) approved Herceptin, a drug that attaches to HER2 and destroys the cell that carries it. One of the first patients to be treated with Herceptin, who had been expected to die within months, is still alive decades later.
Herceptin isn’t the only targeted therapy success story. About 70% of breast cancers are dependent on oestrogen to survive, and many of these cancers, which would invariably have been fatal 30 years ago, are now completely cured by drugs that block the manufacture of oestrogen, or interfere with its action. Similarly, some melanoma patients carry a mutated gene called BRAF-V600E, and drugs such as Zelboraf that attack it have almost doubled survival for these patients. There are lots of other targeted therapies being used in the clinic and even more doing well in clinical trials, and the search continues for targets that are even more specific to cancer cells.
Cancer is a cunning and devious enemy. There will be no single “cure for cancer” because “cancer” is a very large family of very different diseases. Herceptin doesn’t work on every cancer or even on every breast cancer. It only works on cancer cells with HER2.
There are many battles yet to be fought before the war nears an end. But the success and promise of targeted therapies means that we can hope for a future where we will think of cancer as an illness, not a death sentence, and where cancer treatment can be as simple as taking a pill. No sickness, no side effects – and no fear.