There are some 250,000 people in the UK living with blood cancer, a sub-set of the disease that has caught up with 1 in 16 men alive today and 1 in 22 women. Some 40,000 people each year in the UK are diagnosed with blood cancer, and 15,000 people die from it. This makes it the third biggest cancer killer in the UK, after breast and prostate.
It is a strangely intangible disease. Brains, lungs or breasts are easy to understand—we know where they are and what they are there for. By contrast, most of us know very little about our bone marrow, where blood cancer originates, or what our lymph glands do. There are about 100 different sub-categories of blood cancer, many categorised as leukaemia (from the Greek words for white blood) or lymphoma, which strikes in the lymph system.
But precisely because blood is so accessible for testing, this kind of cancer has always been at the forefront of cancer research. “The very first descriptions of genetic abnormalities happened in leukaemia,” says Prof John Gribben, one of the world’s leading blood cancer experts with more than 500 publications to his name. After a long career at Harvard, he is now based at the Barts Cancer Institute in London, specialising in leukaemias and lymphomas. “This led to our first proper understanding of the molecular make-up of cancers, and this in turn led to discoveries in the treatment of solid tumours.”
The breakthrough came in 1959 when researchers David Hungerford from the Fox Chase Center and Peter Nowell from the University of Pennsylvania School of Medicine identified the so-called Philadelphia Chromosome. Named after the city where both were based, this was the first time that a genetic mutation was linked to cancer. Nowell and Hungerford discovered that people with chronic myeloid leukaemia (CML) have one abnormally short chromosome (number 22).
A freakish translocation found to cause cancer
It took more than a decade for scientists to work out precisely what was going on: in the 1970s, Dr Janet Rowley from the University of Chicago demonstrated that the abnormality came about because of a freakish “translocation” of DNA from one gene to another. The new, malfunctioning hybrid gene (called BCR-ABL) switches on the production of cells – and never switches off. “It’s as if the traffic light is constantly on green when it should have been red,” says Gribben. Thus, scientists discovered the first oncogene – cancer gene – that led to a revolution in cancer treatment.
At the time, doctors were relying on chemotherapy – as we have seen a blunderbuss technique that blasts all cells, good and bad – or other drugs that offered short-term respite but not a cure. The prognosis for CML was poor, ditto for acute lymphoblastic leukaemia, where a similar oncogene was found to have a role an aggressive cancer. This is the most common type of the disease to be found in children and younger people. Kids could be offered a bone marrow transplant, a highly risky procedure that up to 50 per cent of patients would not survive. Doctors would be happy if they could keep their patients alive for a year or two after diagnosis. What if you could develop a drug that targeted a specific genetic abnormality?
Imatinib — the first wonder drug
The first of these so-called targeted therapies, aimed at CML and other blood cancers, came to market in 2001. Jointly developed by Drs Brian Druker (of Oregon Health and Science University) and Nicholas Lydon (then working for a drug company that became Novartis), Gleevec (or imatinib) was a wonder drug that had an astonishingly positive impact on patient outcomes. Early trials showed that 98 per cent of people on the drug were in full remission five years after treatment.
“For a lot of people, Gleevec was simply too good to be true. But these once-dying patients were getting out of bed, dancing, going hiking, doing yoga. The drug was amazing,” Dr. Druker said in a 2009 interview with the New York Times.* Now we know that people treated with this drug are as well as people who don’t have cancer at all. There is a more than 90 per cent chance of a full cure for children with acute lymphoblastic leukaemia, and the drug is approved for the treatment of ten different cancers. Not for nothing was this the first cancer drug to feature on the front cover of Time magazine.
It worked by targeting the malfunctioning gene, in effect producing a chemical reaction with the BCR-ABL abnormality, turning the traffic light to red and stopping the ceaseless reproduction of malignant cells. Although the absolute number of people with CML and associated diseases was small, the principle of targeted gene therapy was revolutionary and is at the heart of subsequent advances in the treatment of blood and other cancers.