New drug for cancer in 5 years

Published Date: 04 May 2008
By Kate Foster

THE lives of half of all cancer victims could be saved or prolonged as a result of clinical trials set to start within five years, Scotland's leading researcher in the field revealed last night.

Professor Sir David Lane said work on his earlier discoveries into the link between genes and cancer had reached the stage where drug trials in humans were likely to begin in "four to five years".

Lane, in his first interview since returning to Scotland from a three-year post in Singapore, predicted that if the trials were successful up to 7,000 Scottish cancer sufferers annually could be saved, 10 times as many in the UK and millions across the world.

Lane, who is based at Dundee University, is revered in scientific circles for his discovery of the p53 gene and work on how it helps prevent cancer by "switching off" the damaged cells that can cause tumours.

Speaking exclusively to Scotland on Sunday, he revealed that his own groundbreaking experiments, as well as research by other scientists across the world, had reached a "very exciting" stage.

Many tumours begin when p53 is prevented from doing its vital anti-cancer work by other chemicals in the body. According to Lane, a molecule has been created which allows p53 to carry on fighting the disease. The molecule, Nutlin 3, works by blocking a protein called MDM2 which itself can inhibit p53.

Theoretically, a drug containing Nutlin 3 could be used to help treat virtually all types of cancer, including lung, leukaemia, breast and colon. Approximately half of all cancers involve the p53 gene being blocked by MDM2.

Lane said: "There are things coming to clinical trial soon and that's very exciting. I expect in the next four or five years there will be clinical trials of drugs that work by turning on p53. It's very clear that it's getting very close now and that's a big excitement."

He added: "The thing we would start with would be trials of leukaemia because it's easier to monitor how drugs are working there by taking tumour cells from the blood and seeing if they are being damaged."

Lane predicted: "Cancer will become more and more a treatable disease where the expected outcome is a successful treatment. We are getting towards that already with breast cancer. It's a combination of early detection, trials, and treatments.

"The difference I feel now is that it feels like we are really on the right track. You can feel the progress. There were times 20 years ago when there weren't drugs coming though and this was such a difficult disease to treat. Now we know we are doing the right things. That's not to be complacent because with the ageing population cancer is going to be a major disease but I am really optimistic about what we are doing."

Lane called on the scientific community to work together. "There are a lot of hurdles and the costs go up enormously, hundreds of millions to do full clinical approval, so it's a long staircase," he said. "In the end it's not just one person that gets it there, it's a combination of the scientists, the clinicians, the patients and the public who fund it."

Lane discovered the importance of p53 – since dubbed the 'tumour suppressor gene' or the 'guardian of the genome' – in 1979.

It is hoped that new treatments based on p53 will be more effective and less toxic than traditional therapies such as chemotherapy.

Although cancer deaths are falling in Scotland, the disease remains the nation's biggest killer, claiming 15,000 lives in 2006.

Dr Karen Vousden, director of the Beatson Institute for Cancer Research in Glasgow, said: "There are very few types of cancer that would not be helped by this. It could benefit up to 50% of all cancer cases.

"Potentially this could have an enormous impact. There are still hurdles to overcome. But you can't help but be excited by this."

Andrea Stiglianou, coordinator of the Leukaemia Society, said: "Anything that leads towards better treatments and enables people to lead better quality lives is really gladly welcomed. Sadly, we are still losing patients, so this is welcomed 100%."

Lane has returned to Dundee after three years at Singapore's Institute of Molecular and Cell Biology.

He will now spend most of his time at his research base in Dundee University as well as taking a strategic role with Cancer Research UK, steering its research and investment.

INTERVIEW

'Cancer will become more and more a disease we can treat'

IT STARTED with a conversation over a pint in a Dundee pub more than 15 years ago and could end up saving thousands of lives every year.

David Lane and a colleague dreamed up an experiment that would eventually show how the cancer prevention gene – p53 – worked in humans and open up the possibility of new life-saving treatments.

Now research by one of the world's most famous scientists, Professor Sir David Lane, has taken us to the brink of human trials for drugs that it is hoped will save up to half of all cancer patients.

In an exclusive interview with Scotland on Sunday, 56-year-old Lane has revealed fascinating details of his latest research, and that of other scientists worldwide, and told of his excitement about the prospect of cancer drug trials in as little as four years.

Lane has returned to Dundee University after a working break in Singapore with his wife Birgitte, an eminent scientist in her own right, whose interest is in skin cells.

Despite the string of prestigious awards, his new appointment as chief scientist for Cancer Research UK, and the fact that his work has greatly advanced world science, Lane is unassuming and down-to-earth. When he talks about the mind-boggling potential of his discovery for saving human lives, it is with genuine enthusiasm.

"Cancer will become more and more a treatable disease where the expected outcome is a successful treatment," he said.

"If this work can lead to treatments for half of cancers, I will be a very happy man," he added.

Aside from his own work on p53, Lane is hugely confident about what is happening now in the field of cancer research, with new treatments that target individual cancers.

"There are a lot of active developments happening in the cancer field," he said. "The idea of understanding individual tumours in individual patients is very prominent and many of the new anti-cancer drugs are linked exactly to the particular patient or they are not going to be effective. They are very specific, and that is a challenging process, because we are not just treating everyone with cancer with the same drug.

"They have minor side-effects and are effective. We want more of those and the key is what do you do to make that happen.

"These big successes have come from a breakthrough in basic science understanding, to some translational work to identify the molecules, and finally to the clinical work to make sure it's safe and that the right patients get it."

Returning to his own field of expertise, Lane said that one crucial recent breakthrough was the development of a molecule by US scientists. Developed as a result of his own p53 research, the molecule Nutlin 3, is of growing interest.

Made by Roche pharmaceuticals, Nutlin 3 allows the p53 gene to perform its anti-cancer functions properly by blocking a protein that inhibits the gene.

Lane added that the fact that Nutlin 3 works well has led to "a lot of excitement" in the cancer research field. The next step is to make sure it is safe and effective in humans. Once that has been established, Lane's reputation as one of the world's leading cancer scientists will be assured.

"I am sure it won't work on its own; it will have to be used with other things, but it's a real boost," he added. "We are working on the idea of what combinations work best. We have used it in combination with other molecules and that suggests that using it in combination with other drugs is best."

It has been a long journey for Lane, who, as a 19-year-old science student, witnessed his own father die slowly from bowel cancer. With a younger brother who was aged just six at the time, the experience had a profound effect on him, and he decided, while helping his mother to nurse his father, that if there was anything he could do to help the fight against cancer, he would do it.

And he did. After studying auto-immunity at University College London, he published his 1979 landmark paper on the discovery of p53. It demonstrated that this previously unknown gene played a key role in cancer cells.

At first it was thought the gene actually caused cancer. But further investigations by Lane and a few others over the years revealed it actually did the opposite. In 1990, Lane moved to a post at Dundee University to continue his research, setting up labs funded by Cancer Research UK.

By 1992, much more about the theory of p53 was known because it was fast on its way to becoming the world's most researched gene.

Lane was determined to crack the next big problem: how it worked in the human body. He was so impatient that one evening in a Dundee pub, over a pint, he and a colleague, cancer specialist Peter Hall, dreamed up an experiment – using Hall as the guinea pig – that would avoid the lengthy wait for licensing approvals that human experiments normally require.

The experiment involved subjecting Hall's arm to radiation from a sun lamp, equivalent to 20 minutes on a Greek beach, and taking a series of skin biopsies to watch the activity of p53. They saw what they hoped: the accumulation of p53 in the cells in the radiated skin as it rushed to the rescue of the sun-damaged cells. This finally proved that p53 went to the aid of damaged and potentially cancerous tissue.

Tests involving p53 drugs, however, are currently at the animal stage. But this will change within five years. Lane has previously made the dramatic claim that a 'cure' for cancer will be found within his own lifetime, and he is now on his way to making that claim a reality.

Lane's most recent work involves using zebra fish embryos, which are transparent but have been genetically modified to glow a florescent green when the p53 pathway is switched on. "We can use it to study how drugs interact with p53 and potentially it's a new way of studying how drugs work," he said.

"We are working very closely with others and there are things coming to clinical trial soon that work through this particular pathway and that's very exciting. I expect in the next four or five years there will be clinical trials of drugs that work by turning on p53."

The revelation is a massive boost for Scotland's reputation in scientific research. When Lane left Dundee for Singapore there were concerns that he might not return. But he says he was always going to come back. And it has not only taught him more about cancer, but much about the importance of encouraging scientists.

"It was the spirit of adventure that led me over there," he added. "In my own career it was a good point because my kids had gone to university.

"On a personal level that was a big experience for me, leading 500 scientists in a big institute, and it was jolly hard work. It taught me the lesson that science is dependent upon people and if you want the best scientists your country has to compete with other countries and create attractive environments."

Lane also believes that his new strategic role with Britain's biggest cancer research charity, Cancer Research UK, will allow him to play a role in deciding which projects to fund, and in balancing funding for research with funds for patients.

Around 27,000 Scots were diagnosed with cancer last year, and although some types of the disease, such as cervical and stomach cancer, are decreasing, others, including skin, prostate and breast cancer, are on the rise.

As well as the genetic role of p53, lifestyle factors such as diet, lack of exercise, smoking and alcohol are all known to play a major role. Around 15,000 Scots die from cancer every year.

Ultimately, it is not just his and others' scientific research on finding 'cures' that will help beat cancer, but prevention, screening and early detection.

Lane added: "My job with Cancer Research UK is strategic. We are raising a lot of money from the public and funding places like the Beatson Institute in Glasgow and increasingly supporting translational work for clinical trials. The job is trying to balance these so that we don't put all the money into one thing, such as the university research. Making sure that we support activities in different centres is important.

He added: "If we step back a bit and look at the whole of cancer in society, prevention and early detection is important and the charity has been very active helping to control it.

"Detection is also important, including things like the NHS breast screening programme. This is very exciting; the fact that we are seeing these things rolled out means that we can predict the number of lives that are going to be saved."

Curriculum vitae

PROFESSOR SIR DAVID LANE

Born: Purley, Surrey, 1952.

Educated: Undergraduate and postgraduate degrees at University College London. Post doctoral research at the Imperial Cancer Research Fund in London and the Cold Spring Harbor Labs in New York. Awarded honorary degrees from the universities of Abertay, Stirling, Aberdeen, Birmingham and Nottingham.

Research: Published more than 290 research articles and is internationally recognised for his original discovery of the p53 gene.

Fellowships: Fellow of the Royal Society, the Royal Society of Edinburgh, the Royal College of Pathologists and a founder member of the Academy of Medical Science.

Academic Prizes: Winner of the Joseph Steiner Prize, the Meyenburg Prize, the Yvette Mayent Prize – known as the Nobel Prize of cancer research – and the Paul Ehrlich Prize.

Accolades: Knighted for his contribution to cancer research in the New Year honours list in January 2000.

Employment history: Currently professor of molecular oncology at Dundee University and chief scientist of Cancer Research UK. Former Executive Director of the Institute of Molecular and Cell Biology in Singapore. Founder and former chairman of the Scientific Advisory Board of Cyclacel. Former principal scientist for the Imperial Cancer Research Fund.

Schools need science funds to inspire

SCOTLAND'S future as a nation for groundbreaking research is at risk unless more money is spent on science in schools, Professor Sir David Lane has warned.

Science is hugely encouraged in Singapore schools, with state-of-the-art laboratories and equipment. But schools need to be better funded in Scotland to ensure children are "inspired", he said.

Lane recently spent three years in Singapore on an extended sabbatical, visiting a number of schools to see how science was being taught.

He said he quickly became aware of a difference between the education systems in Scotland and Singapore, and that while top-level university research was comparable in both countries, schools in Singapore were better at teaching science to children.

His comments chime with the results of a recent survey of Scottish schools, which found serious shortcomings in science classrooms, including a lack of equipment and poor assessment.

Lane said: "In Singapore, kids at a young age get good experience of science, and free scholarships are given to the brightest students.

"I noticed the funding for schools and the sense of science being very important for education. A much larger fraction of Singaporean students are trained in science at school than we see in Britain.

"You start to wonder why, and when I visited the schools, the teaching materials were very modern and good, and I don't think that's true in all the schools I have seen in Scotland.

"We need to make sure schools have enough money to do that. Some of these things are happening in Scotland and I hope they continue."

A recent survey by the Save British Science Society found three-quarters of Scottish science teachers warned of a lack of funding for expensive laboratory equipment, and that half of Scottish schools had cancelled practical lessons because of a lack of equipment.