Phyllida Brown, Author at ��è����Ƶ

5. What factors may increase my risk of developing cancer?

6. What are some of the most promising new treatments for cancer?

7. Why does cancer appear so much more common today than in history?

8. Do experts believe we could ever have a universal cure for cancer?

—�Ĕ

Cancer is the uncontrolled growth and spread of abnormal cells. These rogue cells invade and destroy healthy tissues around them. Without treatment, cancer is likely to kill.

For cells to turn cancerous, some of their genes must be damaged through mutation. People may inherit mutations that predispose them to cancer, but damage to genes happens during life too – when cells are exposed to carcinogens such as tobacco, for example. But cells do not easily turn cancerous: at least three “hits”, or different types of damage or mutation, are usually needed.

Three main gene groups are involved in changes that lead to cancer. Firstly, proto-oncogenes normally instruct cells to grow and divide. If these are mutated, they can turn into oncogenes that instruct cells to continue dividing when they should not – imagine a car with the accelerator jammed down. Secondly, tumour-suppressor genes normally stop cells from multiplying. If they are damaged however, like a car brake failing, cell division goes unchecked. The third gene group normally helps in the repair of damaged DNA, but if they fail in their task, cells will copy damaged DNA into their daughter cells as they divide.

Once a cell has transformed into a cancerous state, it begins to divide and multiply. In most cancers, these cells form a lump, or tumour, that can invade surrounding tissue. The tumour puts pressure on healthy cells around it, and may also secrete enzymes to break down that tissue.

By the time a tumour is detected, it will contain billions of cells. Cancerous cells produce growth factors that stimulate blood vessels to grow near them, enabling the tumour to build itself a nourishing blood supply. At later stages of the disease, cells break off the tumour and spread via blood or lymph vessels to seed secondary tumours in other parts of the body.

After heart disease, cancer is the second most common cause of death in Western societies. In your lifetime, the risk of developing some kind of cancer is greater than one in three. There are perhaps 200 different types of cancer, but many are rare.

The most commonly diagnosed are non-melanoma skin cancers, many of which are easily treated. For men, the next most common three types of cancer are prostate, lung and bowel. For women, breast cancer is most prevalent, followed by lung and bowel. The number-one killer among all these is lung cancer, for both men and women. Outside of the West, liver cancer and cervical cancer are among the most common types.

5. What factors may increase my risk of developing cancer?

Cancer is rarely triggered by a single factor. It usually results from an interplay between environmental factors – such as carcinogens or viruses – on one hand, and factors within the body – such as hormones and inherited genes – on the other. Among numerous carcinogens, tobacco towers over the rest as the biggest killer. In the US, for example, it is responsible for 30% of all cancer deaths and 87% of lung cancer deaths. Researchers estimate that a further one-third of cancer deaths can be blamed on other “lifestyle” factors, such as diet and obesity.

Viruses can cause cancer by interfering with the genetic instructions in cells. The worst culprits for this are the hepatitis B virus, which can cause liver cancer, and the human papilloma virus, which can cause cervical cancer. The risk of developing cancer increases with age, simply because cancerous changes in cells usually take years to occur. Two of every three people diagnosed with cancer in the UK each year are over the age of 65.

6. What are some of the most promising new treatments for cancer?

Twentieth-century treatments for cancer – which relied mostly on poisoning tumours through chemotherapy or burning them away with radiation – remain the major weapons in our arsenal. But newer, more sophisticated treatments are starting, slowly, to make an impact. These include:

“Small-molecule” drugs that interfere with the signals inside cancer cells. One such drug is Glivec (Gleevec in the US), or imatinib, which targets abnormal proteins that instruct cancer cells to grow. Glivec is used to treat one type of leukaemia and a rare tumour of the gut.

A compound called 17AAG, which is in UK trials with people with malignant melanoma and a range of other tumours. 17AAG works by stopping a protein called Hsp90 from working.

Drugs that tell cancer cells to commit suicide, or apoptose. One, called Velcade or bortezomib, is approved in the US for people with a type of cancer called multiple myeloma.

Drugs that block the growth of new blood vessels around a tumour, so that the tumour starves. Avastin, or bevacizumab, has prolonged life for people with bowel cancer.

Monoclonal antibodies that block cancer cells by binding to the specific proteins they need to spread. For example, Herceptin, or trastuzumab, is being used to treat women with breast cancer.

7. Why does cancer appear so much more common today than in history?

More people are surviving into old age – not only in industrialised countries but worldwide – so there are more cases of cancer. As non-Western nations such as China and India smoke ever-more tobacco, worldwide prevalence could soar to a projected 16 million cases per year by 2020 – compared with 11 million cases today.

8. Do experts believe we could ever have a universal cure for cancer?

No. There are so many different types of cancer, and so many causes, that the idea of a universal cure is too simplistic. However, many experts are hopeful that a combination of better treatments and earlier detection, could whittle down death rates significantly. Some experts talk about “managing” cancer so that it becomes a chronic long-term condition, and not a direct threat to life.

Introduction: Cancer

Phyllida Brown — Mon, 04 Sep 2006 10:45:00 +0000

Cancer is a group of over one hundred diseases, all of which share the common feature of uncontrolled spreading of malignant cells in the body

(Image: Science Source / Science Photo Library)

One in three of us will get cancer at some point in our lives. Once so feared its name was whispered, the disease is no longer an inevitable death sentence. Today, almost two-thirds of those who develop cancer will still be alive five years later, compared with just half in the 1970s.

Cancer has turned out to be tougher to crack than everyone hoped when US President Richard Nixon launched the War on Cancer in 1971. But death rates are falling, thanks to earlier detection of tumours and improved use of existing treatments – mainly chemotherapy and radiotherapy. The success has been biggest for children: since the mid-1970s, death rates from cancers of childhood have halved. Of those with the most common childhood cancer, acute lymphocytic leukaemia, 85% are still alive five years later, compared with just 53% in the 1970s.

Inner workings

A key reason why cancer patients are living longer, is that scientists now understand more clearly what happens when cells turn cancerous. Cancer begins when genes which normally control cell division, growth and repair are damaged through mutation. These genes can then cause cells to grow and divide uncontrollably, destroying neighbouring healthy cells. For example, a gene called p53, which normally acts as a brake on cell division, turns out to be mutated or lost in about half of all tumours. Another proto-oncogene, Myc normally helps healthy cell division, but can become an oncogene if damaged, causing cells to divide unchecked.

Mutations can arise by chance errors in DNA replication, and genes can also be damaged by carcinogens – such as tobacco chemicals, benzene, possibly acrylamide and some food additives – or ultraviolet light from sunshine. Certain viruses can also trigger gene mutations, such as the human papilloma virus that can cause cervical cancer.

Some mutated genes are inherited: two examples are BRCA1 and BRCA2, which together account for about 5% of all breast cancer cases. Other genes such as DBC2, EMSY and FA have been implicated in ovarian, breast and lung cancer.

Once a cell has turned cancerous, it divides until a mass of cells forms a tumour. Diagnostic tests can quickly distinguish between malignant, or cancerous, tumours and those that are benign, or harmless. As a malignant tumour progresses, cells or clumps of cells break off and spread, or metastasise, around the body via the lymphatic system and blood vessels.

The latest generation of treatments exploit our knowledge of what happens within cancerous cells. These target proteins and messenger chemicals – such as growth factors or enzymes – that the errant cells need to survive and grow.

Glivec (or Gleevec), for example, targets abnormal proteins that help cancerous cells to grow. Dubbed the first “magic bullet” for cancer, it is used to treat one type of leukaemia and a rare cancer of the gut. Another drug, 17AAG, targets cancer cells by suppressing Hsp90 – a protein vital for their growth. The drug is undergoing trials to treat melanoma and other cancers that affect the prostate, kidney and breast.

An alternative approach is to persuade the immune system to attack tumours, using vaccines, biological therapies such as alpha interferon or interleukin 2 and genetically altered white blood cells. In the future, scientists hope to target stem-cell-like cells within cancers that may be responsible for most of the growth of some tumours, and evade existing drugs. They also plan to use nano-drugs, nano-bullets and “smart bombs” to deliver molecules with pinpoint precision to tumour cells.

Even soil-living or flesh-eating bacteria, engineered viruses, weed extracts, microwaves, chemicals from Antarctic sea squirts and the immune cells of siblings have been recruited to destroy tumours.

Prevalence Patterns

In developed countries, the cancer most likely to afflict you is non-melanoma skin cancer, often caused by the Sun’s harmful ultraviolet rays. This is usually treated and cured. Melanoma, a deadlier skin cancer, is less common but is increasing by around 3% a year in the US. Though UV light is the cause of many skin cancers, there is some evidence that small amounts may also help prevent other cancers. In the developing world the most common cancers are linked to infectious agents, such as cervical cancer or liver cancer, caused by hepatitis B.

The biggest killer in industrialised nations remains lung cancer. For men, lung cancer mortality has been falling since 1990, mirroring a peak in popularity of smoking during the 1960s. For women, who commonly took up smoking later, lung cancer mortality is still rising. Tobacco is also rapidly becoming the leading cause of cancer in Asia.

Breast cancer accounts for almost one in three of all cancers diagnosed in women each year. For men, prostate cancer is just as common, with the highest rates in African American men and Caribbean men of African origin.

Screening for both of these diseases has improved sharply. Early breast tumours show up on a mammogram long before they can be felt as a lump. More women now survive the disease – three-quarters of women whose breast cancer was diagnosed 10 years ago are still alive today. Similarly, a prostate-specific antigen (PSA) test has revolutionised early diagnosis for this cancer in the US. Some experts argue that screening can be harmful, however.

Factoring in risk

Dozens of factors affect an individual’s risk of getting cancer. Smoking is the biggest single risk factor – with tobacco linked to about a third of all cancers.

Another clearly established risk factor is exposure to ionising radiation. This may be responsible for cancers in people living around Chernobyl in Ukraine, Toikamura in Japan and for people working in nuclear power plants. Radiation may also have led to a high incidence of cancer in those who witnessed early nuclear tests or have been in contact with depleted uranium munitions, though a recent study contests this risk.

Risk factors for developing breast cancer include: being childless or delaying childbearing until aged over 30, starting periods early, using hormone replacement therapy, being exposed to oestrogen-like chemicals, and drinking one or more units of alcohol daily. More than one risk factor is usually needed before cancer cells develop.

Risks posed by living near overhead power lines or petrol stops, or using cellphones, are less clear.

Preventative steps

If everyone stopped smoking, cancer deaths could be cut by one-third, researchers estimate. Moves to protect people from passive smoking, in bars for example, are gaining ground in many industrialised countries.

Staying out of sunlight and using strong sunscreens could prevent hundreds of thousands of us from developing skin cancer worldwide annually. Foods rich in antioxidants and beneficial fatty acids such as omega-3 and oleic acid found in olive oil – a key ingredient of the healthy Mediterranean diet – seem to protect against some cancers, although the findings are mixed.

Doctors can increasingly intervene directly to prevent cancers. For example, vaccines against hepatitis B could soon cut deaths from liver cancer. There are also preventive therapies – such as tamoxifen or the trial drug anastrazole – that interfere with the production of the hormone oestrogen, implicated in many breast cancers. Doctors believe that it could halve the rates of breast cancer in women with a family history of the disease.

All this means that, while hopes of total cure for cancer are still unrealistic, the disease is increasingly under control.

FAQ: Cancer

Phyllida Brown — Mon, 04 Sep 2006 10:42:00 +0000

Cancer – Learn more about one of the world’s biggest killers in our comprehensive special report.

5. What factors may increase my risk of developing cancer?

6. What are some of the most promising new treatments for cancer?

7. Why does cancer appear so much more common today than in history?

8. Do experts believe we could ever have a universal cure for cancer?

—�Ĕ

Cancer is the uncontrolled growth and spread of abnormal cells. These rogue cells invade and destroy healthy tissues around them. Without treatment, cancer is likely to kill.

Three main gene groups are involved in changes that lead to cancer. Firstly, proto-oncogenes normally instruct cells to grow and divide. If these are mutated, they can turn into oncogenes that instruct cells to continue dividing when they should not – imagine a car with the accelerator jammed down. Secondly, tumour-suppressor genes normally stop cells from multiplying. If they are damaged however, like a car brake failing, cell division goes unchecked. The third gene group normally helps in the repair of damaged DNA, but if they fail in their task, cells will copy damaged DNA into their daughter cells as they divide.

5. What factors may increase my risk of developing cancer?

6. What are some of the most promising new treatments for cancer?

A compound called 17AAG, which is in UK trials with people with malignant melanoma and a range of other tumours. 17AAG works by stopping a protein called Hsp90 from working.

Drugs that tell cancer cells to commit suicide, or apoptose. One, called Velcade or bortezomib, is approved in the US for people with a type of cancer called multiple myeloma.

Drugs that block the growth of new blood vessels around a tumour, so that the tumour starves. Avastin, or bevacizumab, has prolonged life for people with bowel cancer.

Monoclonal antibodies that block cancer cells by binding to the specific proteins they need to spread. For example, Herceptin, or trastuzumab, is being used to treat women with breast cancer.

7. Why does cancer appear so much more common today than in history?

8. Do experts believe we could ever have a universal cure for cancer?

Head of the Wellcome Trust describes his vision

Phyllida Brown — Wed, 30 Aug 2006 18:00:00 +0000

HIGH above a roaring central London, Mark Walport’s calm, glass-walled office feels like an eyrie, designed for serious, uncluttered thinking. Behind him are treasures from the collection of Sir Henry Wellcome, founder of the charity that Walport now directs. But it’s the view of the city, across a tangle of rooftops and glinting high-rises, that dominates.

The office seems to symbolise the fresh approach he’s bringing to the 70-year-old trust, one of the world’s biggest funding charities, with more than £400 million to spend on bioscience research each year.

Not long ago, the trust had a reputation for being inscrutable and high-handed, and it seemed to have no need to justify its decisions to the outside world. Under Walport, the trust is fast becoming more open and accountable: “The world has changed completely, we are much more transparent than in the past.” His enthusiasm for his role, which includes running the trust and engaging in high-profile public debates, is obvious. “I suppose I like managing quite complicated things,” he says. He has the relaxed but energetic air of someone who relishes difficult questions – and the yellow shirt and blue-and-red spotted braces show a sense of fun, too.

The world has changed completely, we are much more transparent than in the past

Back in 1992, when ��è��Ƶ interviewed a previous incumbent, Bridget Ogilvie, in the old building, it was like being sent to the headmistress. This is worlds away. Part of the change is the architecture of the new headquarters. Opened in 2004, the Gibbs Building is all open space and cathedral-like proportions. Its centrepiece is a seven-storey-high sculpture based on a falling drop of molten metal by the British sculptor Thomas Heatherwick, which he calls Bleigiessen, or “lead-pouring”, after a New Year’s Eve fortune-telling activity in central Europe.

Another part of the change is about coming of age. “As people become more confident they tend to become more transparent,” says Walport, who stresses that change had begun before he took over in 2003. Just five years ago, for example, Sir Henry’s will was transformed into a modern constitution, in line with UK charities law. The trust, Walport believes, had to deal with the impact of its own growth in the early 1990s, after it sold its shares in the pharmaceuticals company Wellcome and doubled its research budget overnight (��è��Ƶ, 1 August 1992, p 12). Only then could it become more outward-looking.

As director, Walport must answer to the governing board. This formerly exclusive group is now “very strong, properly structured and very challenging”, he explains. Governors must apply for their posts, which are publicly advertised, with headhunters also involved in seeking high-calibre candidates. All governors post their biographies and photos on the trust’s website. “The executive running a fairly big organisation needs to be challenged, to be asked very difficult questions,” says Walport, adding that some government departments would benefit from such accountability.

Walport’s career was not planned. He read medicine at the University of Cambridge and the Middlesex Hospital Medical School in London. After working as a junior doctor in London, he returned to Cambridge to do a PhD under immunologist Peter Lachmann, who proved a great mentor. Lachmann invited him to stay in his group, but Walport felt like branching out, and took a senior lectureship at the Royal Postgraduate Medical School (RPMS) in London’s Hammersmith Hospital.

There, Walport pursued immunology and rheumatology, becoming professor of medicine and then head of research for RPMS. By 1994, he had been appointed vice-dean, and three years later, chair of the division of medicine. During his time as chair, he managed the complex merger of the RPMS with Imperial College, London. He also had a spell as a governor of the Wellcome Trust, which taught him about the charity. So when the Wellcome Trust’s previous director, Mike Dexter, left, Walport decided to apply.

His enthusiasm is driven in part by the same fascination with science that motivated him since boyhood. “I was interested in bugs, beetles and birdwatching as a child. I have always liked discovering things by doing experiments.” Now he delights in reading applicants’ ideas : “It’s fun. It’s a continuous free education looking at the creative thoughts of people from right across science.”

Beyond the fun, Walport has a firm grip on a restructured budget. In the past, funding was driven by process. He argued instead for a science-led framework, and in 2004 the trust set up six funding streams: one in medical humanities and five in biomedicine. Each stream has a committee of leading external scientists who advise on how best to develop areas of research and training, and at least one funding committee that awards grants. The governors make major funding decisions.

Good returns

Walport is also trying to change how the trust evaluates the returns. At present, most funding bodies focus on the quality of grant applications when they decide which work to support. Increasingly, he believes, funding bodies should review work afterwards too. Making this happen is not straightforward. Should research funding bodies be more like businesses? After all, the world’s biggest health-research charity, the Bill and Melinda Gates Foundation, makes clear that it expects applicants to deliver, and that it will require answers to its questions. Walport is open to ideas, though he warns against simplistic measures. He rejects, for example, the “mindless use” of bibliometric techniques, where applicants’ publications are simply counted and weighted for the journal’s impact factor without regard to subtleties. For instance, he says that many papers in the highest-impact journals are never cited, while other papers have impact by influencing clinical practice but yet are not cited.

What’s more, the benefits of a scientific discovery are not always immediately apparent. Walport cites the use of ultrasound as a tool in antenatal medicine. One of its pioneers, Scottish obstetrician Ian Donald, had developed an interest from his knowledge of sonar in submarines and shipbuilding. “You could do any citation analysis you like,” says Walport, “and not discover that.”

Walport believes that his time as a doctor has influenced his leadership style. He was attracted to rheumatology because of its complexity: “The critical thing about being a good doctor is to work out the important problems so you can analyse the causes and find solutions.” This also applies to managing a large organisation, he believes.

Equally, he feels his time as a scientist gives him insight into the researchers they fund. He knows well the effort that goes into grant applications, for example, and feels that researchers should always be able to find out why they failed. Back in 1992, Wellcome did not explain why it rejected applications.

He also thinks that the trust has a vital role to play in the public arena. Recently, Walport pushed hard for scientists to regulate their own work so they can continue studying the pathogens and toxins terrorists might abuse. Without self-regulation, he fears, key research could be shut down. Walport is also a big player in helping create free online access to scientific papers. The trust must speak out, he says, because it is seen as independent and essentially benevolent.

The pace of activity shows no sign of letting up. At the end of July, the trust announced plans for a £10 million centre for stem cell research in Cambridge, funded with the Medical Research Council and the Wolfson Institute for Biomedical Research. Such partnerships, once unheard of, are becoming normal: openness, it seems, is now for real.

CV – Mark Walport

1974: BA in medical science and natural sciences (pathology) from the University of Cambridge
1977: qualified as a doctor at the Middlesex Hospital Medical School, London
1980: Member of the Royal College of Physicians
1982: Medical Research Council training fellow in the MRC Mechanisms in Tumour Immunity Unit, Cambridge
1986: PhD in immunology, University of Cambridge
1985: Head of rheumatology section, Royal Postgraduate Medical School of London
1990: Fellow of the Royal College of Physicians
1991: Professor of medicine, head of rheumatology, Royal Postgraduate Medical School of London
1994: Director of research and development, The Hammersmith Hospitals NHS Trust
1994: Vice-dean (research), Royal Postgraduate Medical School of London
1997: Professor of medicine, chairman of the division of medicine, Hammersmith Hospital, Imperial College, London
2000-2003: Governor, the Wellcome Trust
2003: Director, the Wellcome Trust

Sobering news for pregnant women

Phyllida Brown — Wed, 28 Jun 2006 18:00:00 +0000

Surely an occasional drink during pregnancy can't do any harm? Don't be so sure

FAQ: Cancer

Phyllida Brown — Tue, 09 Aug 2005 10:17:00 +0000

5. What factors may increase my risk of developing cancer?

6. What are some of the most promising new treatments for cancer?

7. Why does cancer appear so much more common today than in history?

8. Do experts believe we could ever have a universal cure for cancer?

—�Ĕ

Cancer is the uncontrolled growth and spread of abnormal cells. These rogue cells invade and destroy healthy tissues around them. Without treatment, cancer is likely to kill.

For cells to turn cancerous, some of their genes must be damaged through mutation. People may inherit mutations that predispose them to cancer, but damage to genes happens during life too – when cells are exposed to carcinogens such as tobacco, for example. But cells do not easily turn cancerous: at least three hits, or different types of damage or mutation, are usually needed.

5. What factors may increase my risk of developing cancer?

6. What are some of the most promising new treatments for cancer?

Small-molecule drugs that interfere with the signals inside cancer cells. One such drug is Glivec (Gleevec in the US), or imatinib, which targets abnormal proteins that instruct cancer cells to grow. Glivec is used to treat one type of leukaemia and a rare tumour of the gut.

A compound called 17AAG, which is in UK trials with people with malignant melanoma and a range of other tumours. 17AAG works by stopping a protein called Hsp90 from working.

Drugs that tell cancer cells to commit suicide, or apoptose. One, called Velcade or bortezomib, is approved in the US for people with a type of cancer called multiple myeloma.

Drugs that block the growth of new blood vessels around a tumour, so that the tumour starves. Avastin, or bevacizumab, has prolonged life for people with bowel cancer.

Monoclonal antibodies that block cancer cells by binding to the specific proteins they need to spread. For example, Herceptin, or trastuzumab, is being used to treat women with breast cancer.

7. Why does cancer appear so much more common today than in history?

8. Do experts believe we could ever have a universal cure for cancer?

No. There are so many different types of cancer, and so many causes, that the idea of a universal cure is too simplistic. However, many experts are hopeful that a combination of better treatments and earlier detection, could whittle down death rates significantly. Some experts talk about managing cancer so that it becomes a chronic long-term condition, and not a direct threat to life.

Phyllida Brown, 9 August 2005

FAQ: Cancer

Phyllida Brown — Thu, 21 Jul 2005 14:06:00 +0000

5. What factors may increase my risk of developing cancer?

6. What are some of the most promising new treatments for cancer?

7. Why does cancer appear so much more common today than in history?

8. Do experts believe we could ever have a universal cure for cancer?

—�Ĕ

Cancer is the uncontrolled growth and spread of abnormal cells. These rogue cells invade and destroy healthy tissues around them. Without treatment, cancer is likely to kill.

For cells to turn cancerous, some of their genes must be damaged through mutation. People may inherit mutations that predispose them to cancer, but damage to genes happens during life too – when cells are exposed to carcinogens such as tobacco, for example. But cells do not easily turn cancerous: at least three hits, or different types of damage or mutation, are usually needed.

5. What factors may increase my risk of developing cancer?

6. What are some of the most promising new treatments for cancer?

A compound called 17AAG, which is in UK trials with people with malignant melanoma and a range of other tumours. 17AAG works by stopping a protein called Hsp90 from working.

Drugs that tell cancer cells to commit suicide, or apoptose. One, called Velcade or bortezomib, is approved in the US for people with a type of cancer called multiple myeloma.

Drugs that block the growth of new blood vessels around a tumour, so that the tumour starves. Avastin, or bevacizumab, has prolonged life for people with bowel cancer.

Monoclonal antibodies that block cancer cells by binding to the specific proteins they need to spread. For example, Herceptin, or trastuzumab, is being used to treat women with breast cancer.

7. Why does cancer appear so much more common today than in history?

8. Do experts believe we could ever have a universal cure for cancer?

No. There are so many different types of cancer, and so many causes, that the idea of a universal cure is too simplistic. However, many experts are hopeful that a combination of better treatments and earlier detection, could whittle down death rates significantly. Some experts talk about managing cancer so that it becomes a chronic long-term condition, and not a direct threat to life.