Category Archives: Scientific papers

Melanoma genome reveals UV damage and treatment targets

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The sun

Researchers have finally pinned down the link between UV radiation and gene faults that drive melanoma. Image source: Wikimedia Commons

We all need a bit of sunshine in our lives – something that’s often lacking in the Great British Summer.

But while UV light (radiation) from the sun helps our bodies to make vitamin D, which is vital for building healthy bones, there’s a dark side to UV. It damages our DNA – the genetic ‘instruction manual’ in all our cells – which increases the risk of skin cancer.

Researchers have shown that eight out of 10 cases of malignant melanoma – the most dangerous form of skin cancer – are caused by getting too much UV, either from the sun or sunbeds. There’s also good evidence from population studies to show that getting sunburned at any age doubles the risk of developing melanoma later in life, and people who have the highest levels of UV exposure also have a higher skin cancer risk.

But up until now, there’s been an inconvenient problem for researchers studying precisely how UV-induced DNA damage leads to skin cancer: the major gene faults known to be involved in melanoma don’t actually show the hallmarks of UV damage. And because UV can cause such widespread damage throughout our genome, it’s been hard to pin down exactly which other genes might be involved in the disease.

Thanks to the advent of high-tech genome sequencing technology, this conundrum may have now been solved by two research teams in the US. Their results prove beyond doubt that UV-induced genetic damage can drive the development of melanoma, and highlight important new targets for future treatments for the disease.

Let’s take a closer look at what they found.

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Cannabis, cannabinoids and cancer – the evidence so far

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An illustration of cannabis plants

Cannabis has long been used for medicinal as well as recreational purposes. Image source

Few topics spark as much debate on this blog and on our Facebook page than cannabis.

So we thought we’d take a look at the common questions raised about the evidence and research into cannabis, cannabinoids (the active chemicals found in the plant and elsewhere) and cancer, and address some of the wider issues that crop up in this debate.

We’ve broken it down under a number of headings:

This post is long, but can be summarised by saying that at the moment there isn’t enough reliable evidence to prove that cannabinoids – whether natural or synthetic – can effectively treat cancer in patients, although research is ongoing around the world.

Read on to get the full picture.

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Could a blood test reveal cancer’s genetic secrets?

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A nurse taking a blood sample

A simple blood test might one day help doctors monitor the genetic changes in cancer in ‘real time’

Over recent months we’ve written about exciting new research looking at how the genetic makeup of an individual patient’s cancer shifts and evolves as the disease develops and spreads.

At the moment the only way to monitor this is to take a sample of a tumour (called a biopsy) and test it in the lab. But this approach isn’t perfect – for a start, a doctor needs to be able to reach a tumour in order to take a biopsy, which often has to be done surgically. And monitoring the disease over time means repeated biopsies, which may need to be taken from multiple places if the cancer has spread.

Wouldn’t it be fantastic if there was a simple blood test that could reveal the genetic fingerprints of a tumour, no matter where it’s located in the body?

This solution may be closer than you think. Although it’s still at an early stage and needs more work, scientists at our Cambridge Research Institute have developed a blood test that can detect genetic mutations in tiny fragments of DNA shed into the bloodstream by dying cancer cells. And it has the potential to be a game-changer for the way the disease is monitored and treated – and maybe even diagnosed – in the future.

Here’s a short video of study leaders Dr Nitzan Rosenfeld and Dr James Brenton, explaining more about their exciting research and what it might mean for cancer patients in the future.

The Cambridge team has just published their results in the journal Science Translational Medicine, so let’s look in a bit more detail about how the test works and where this research might take us in the future.

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‘Sleeping Beauty’ reveals new pancreatic cancer genes

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Sleeping Beauty

A ‘jumping gene’ called Sleeping Beauty has revealed new hope in understanding pancreatic cancer

Over recent decades we have made huge progress in survival for many types of cancer, including breast, bowel, testicular, and prostate cancer as well as childhood cancers.

But some types of cancer – including pancreatic, lung, and oesophageal cancers, as well as brain tumours – have remained stubbornly resistant to dedicated efforts of scientists and doctors to improve the situation.

We believe the key to beating cancer is through research – to know what causes the disease in the first place, what drives it to grow and spread, and how best to target it with different treatments. And it’s by working harder to understand these cancers with poor survival rates that we can change the outlook for patients.

Now scientists at our Cambridge Research Institute and the Wellcome Trust Sanger Institute have made an important step forward in understanding one of the most challenging forms of pancreatic cancer.

The researchers have hunted down a crucial gene involved in the disease and, publishing their results in the prestigious scientific journal Nature, have also revealed a potential way to target it.

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Increasing the resolution on breast cancer – the METABRIC study

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A breast cancer cell

New research has examined breast cancer in even more detail

The emotion and anxiety aroused by a single word – ‘cancer’ – spans ages, sexes, nations, races and classes.

But as we understand more about the disease, the idea that cancer is a single, common enemy, is increasingly being challenged.

In late 2009, the publication of the first complete cancer genomes showed the extraordinary chaos present in the DNA inside cancer cells. But they also highlighted the molecular differences between different types of cancer – in this case, skin cancer and lung cancer

Other large gene studies have revealed even more differences between types of cancer, but have also increased out understanding of the differences between the ‘same’ cancer type in different people – the foundation of ‘personalised medicine’.

For example, last week a team of Canadian and British researchers, writing in the journal Nature, analysed the DNA from 104 ‘triple-negative’ breast cancers – a particularly hard-to-treat form of the disease.

As this in-depth post on the Respectful Insolence blog describes, they found that no two women’s cancers were alike – there were differences across all the tumour samples. Even a subcategory like ‘triple-negative’ breast cancer doesn’t seem to be a single disease (a point we’ll return to later). And genetic differences also appeared between cells from the same tumour – known as ‘intratumour heterogeneity’.

This point was emphasised a few weeks earlier by researchers at our London Research Institute. They analysed multiple samples from the same patient’s kidney tumour and secondaries (where the cancer had spread to other parts of the body).

No two samples were identical, suggesting that there’s significant variation even inside a tumour. As we discussed in this blog post, it looks like tumours can be highly varied, creating new challenges in the search for personalised medicine.

A video about METABRIC

A video about METABRIC (click to open in a new window)

Which brings us to today’s news, of a landmark Cancer Research UK-funded study published in Nature.

Through intricate genetic analysis, the same British and Canadian researchers, led by Professor Carlos Caldas from our Cambridge Research Institute and Professor Sam Aparicio from the British Columbia Cancer Centre in Canada, have uncovered crucial new information about breast cancer.

Their study group, METABRIC (Molecular Taxonomy of Breast Cancer International Consortium), looked at the patterns of molecules inside tumours from nearly two thousand women, for whom information about the tumour characteristics had been meticulously recorded.

They compared this with the women’s survival, and other information, like their age at diagnosis.

While many other studies have highlighted differences between cancers, the METABRIC study looked at so many tumours that they could spot new patterns and ‘clusters’ in the data.

Their conclusion is that what we call ‘breast cancer’ is in fact at least ten different diseases, each with its own molecular fingerprint, and each with different weak spots.

This is simultaneously daunting and heartening – daunting because each of these diseases will likely need a different strategy to overcome it; and heartening because it opens up multiple new fronts in our efforts to beat breast cancer.

Let’s look at the background to the study, then in detail at what the researchers actually did, what they found, and what this means for the future of breast cancer treatment and diagnosis.

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Shattered chromosomes give clue to childhood medulloblastoma and neuroblastoma

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Shattered glass

Shattered chromosomes have been implicated in two types of childhood cancer.

Last year, the surprising discovery of chromothripsis– literally translated as “chromosome shattering” – revealed an entirely novel way for the DNA in cancer cells to get messed up, and opened the door to new ideas about how tumours develop and progress.

Unlike the slow and steady march of DNA damage that characterises many tumours – like the accumulation of typos in a recipe book – researchers found that some cells were experiencing a single episode of genetic vandalism on a grand scale. Their ‘recipe book’ was being torn to pieces and glued back together in a random and haphazard way.

Scientists around the world have been delving further into this phenomenon over the past year. And chromothripsis has now been found in a small but significant percentage of different types of cancer, notably leukaemias and multiple myeloma.

Now two recent papers from international research groups show that chromothripsis may be an important event during the development of two types of childhood cancer – medulloblastoma (the most common type of brain tumour in children), and neuroblastoma, which affects nerve tissue outside the brain.

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On the origin of tumours

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Darwin's first sketch of an evolutionary tree, from 1837

Researchers now think tumours evolve in a Darwinian fashion

“Cancer starts when a single cell in our body starts dividing out of control.”

We repeat this statement so often it would be banal, were it not for its implications.

But after a single, initial, malignant cell division, what happens to the two resulting ‘daughter’ cells? Are they identical to their parents? And what about their daughters? And their daughters’ daughters?

And what about the offspring that split off and travel around the body? After all, it’s usually cancer’s tendency to spread that makes it dangerous, rather than the initial tumour itself. But why is it that advanced cancer is so hard to treat?

Today, a team of some of the UK’s most exciting young researchers, funded by Cancer Research UK, University College London Cancer Institute, the Medical Research Council and the Wellcome Trust, has published results of a three-year analysis of kidney cancer samples.

Sequencing billions of ‘letters’ of DNA, the researchers looked in unprecedented detail at the relatedness of different regions of patients’ tumours, and between the patients’ primary tumour and the more distant secondaries, or ‘metastases’.

Their findings are stark: whichever way they looked at the data, no two samples from the same patient were genetically identical – not even samples next to each other in the original tumour. And the secondaries were significantly different from their parent tumour.

Their findings are the most compelling evidence yet that, like populations of animals in an ecosystem, tumours adapt as they grow, obeying the fundamental evolutionary laws laid down by Charles Darwin over a century ago. It seems this evolutionary aptitude may foster their ability to spread, and to become resistant to almost every treatment we can throw at them.

This heterogeneous nature of cancer has big implications for the way we think about the disease, and for how we continue to improve the way we treat it.

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