High-Impact Science - Cancer Research UK

Tamoxifen – the start of something big

Posted on October 15, 2012 by Emma Smith

This entry is part 11 of 12 in our High-impact science series

We helped shape how tamoxifen is used

Bringing a new drug to patients is a long and winding road. But the journey doesn’t stop once a drug is approved for use – researchers continue to study and refine how best to give it to patients.

The latest in our High Impact Science series is the story of tamoxifen, a discovery in 1966 that has gone on to save the lives of millions of women with breast cancer.

The background

Around 8 in every 10 breast cancers diagnosed in the UK are classified as ‘oestrogen receptor-positive’ (or ER positive for short). The cancer cells in ER-positive tumours contain large quantities of a protein called the oestrogen receptor. This means the tumours grow in response to the female hormone, oestrogen, which circulates in a woman’s bloodstream.

Being dependent on oestrogen gives ER-positive cancers an Achilles heel: it makes them sensitive to drugs like tamoxifen, which block oestrogen from affecting cancer cells.

Tamoxifen works like a broken key in a lock – it sticks to the oestrogen receptor, preventing the normal ‘key’ (oestrogen) from fitting anymore, thereby stopping the tumour in its tracks. Its precision targeting of ER-positive breast cancer cells in this way mean it is, in effect, a ‘targeted treatment’.

Since its approval in the UK in 1972, tamoxifen’s effectiveness and affordability have earned it a place on a global stage – it appears on the World Health Organisation’s list of essential drugs for the treatment of breast cancer in both developing and developed countries. So, how was this widely used, remarkable drug discovered?

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Hedgehogs, flies and skin cancer – the story of vismodegib

Posted on June 7, 2012 by Safia Danovi

This entry is part 10 of 12 in our High-impact science series

Professor Phil Ingham, whose Cancer Research UK-funded work in the 1990s has led to a new skin cancer drug

The course of drug development never did run smooth. Drug development pipelines – like the X-Factor – are littered with thousands of ‘hopefuls’ who fail to make the cut.

Very few drugs survive the arduous journey from bench to bedside, and those that do often emerge ten to twenty years later, bearing little resemblance to their former selves.

In fact, only about one in ten drugs initially tested in patients make it through to routine use. So it’s always good news when an experimental drug makes it all the way through the difficult journey of tests and clinical trials.

As we reported this morning, vismodegib – a skin cancer drug that our work helped shape – is described as “the greatest advance in therapy yet seen for this disease” in the prestigious New England Journal of Medicine – extremelyexciting news.

So in the latest of our ‘High-Impact Science’ blog posts, we’d like to tell the story of Professor Phil Ingham, and how his fundamental research in fruit flies and fish evolved into a drug that could revolutionise treatment for patients with advanced basal cell carcinoma – a type of skin cancer.

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Tracking down the BRCA genes (Part 2)

Posted on February 29, 2012 by Kat Arney

This entry is part 9 of 12 in our High-impact science series

Professor Mike Stratton led the team that tracked down BRCA2

In part one, we told the story of Cancer Research UK’s involvement in the race to identify BRCA1 – the first known breast cancer gene.

Although this was a very important discovery, it wasn’t the end of the story. Along the way, researchers had discovered evidence suggesting that there had to be at least one more gene out there.

Here we look at how our scientists revealed the identity of the second breast cancer gene, BRCA2, and what the discovery of both these genes means for cancer patients and their families.

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Tracking down the BRCA genes (Part 1)

Posted on February 28, 2012 by Kat Arney

This entry is part 8 of 12 in our High-impact science series

Cancer Research UK’s Professor Doug Easton is one of the researchers who helped to track down BRCA1

In this two-part post in our High-Impact Science series we look at Cancer Research UK’s role in the discovery of two of the most famous “cancer genes” known to science – BRCA1 and BRCA2.

Faults in these genes are responsible for most cases of hereditary breast cancer (around 5 per cent of all breast cancers), as well as inherited ovarian and prostate cancers, and possibly more.

Thanks to the discovery of these genes, women at high risk of breast and ovarian cancer can now be offered genetic testing, along with lifesaving advice about prevention and screening for these diseases. And our scientists have been there all the way.

On your marks…

The starting line for the hunt for BRCA1 and BRCA2 was drawn back in the 1940s, before we fully understood how genes and DNA work.

British researcher Sir David Smithers, from the Royal Free Cancer Hospital, published a paper looking at the family trees of more than 450 breast cancer patients. He showed that breast cancer could occasionally run in families, with several relatives being affected by the disease across the generations.

Over the next few decades, as our picture of how genes work grew clearer, it became obvious that these hereditary cases of breast cancer were caused by a faulty gene or genes.

By the 1980s, as the genes involved in cancer were gradually revealed, this conundrum of inherited breast cancer was thrown into sharper focus. What were these genes, and what did they do?

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A story of Myc and death

Posted on January 25, 2012 by Kat Arney

This entry is part 7 of 12 in our High-impact science series

Professor Gerard Evan’s work turned our understanding of a crucial cancer gene on its head

In this next post in our High-Impact Science series, we look at a rather surprising discovery made by Professor Gerard Evan and his team at the Cancer Research UK London Research Institute in the early 1990s.

Their results overturned established thinking, leading to a massive leap in our understanding of the intricate mechanisms that drive cancer and ultimately paving the way for new treatments

It all centres on a gene called Myc, which was known to be an “accelerator” gene (oncogene), responsible for driving the growth of cancer cells. But Professor Evan and his colleagues showed that Myc could also cause cancer cells to die – the complete opposite of what was expected. The scientists published their findings in the journal Cell in 1992, shaking up the whole field of cancer research in the process.

Let’s look in a bit more detail about how the team revealed Myc as both a bringer of cell life and cell death, and why it was so important.

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Chasing down the APC bowel cancer gene

Posted on November 29, 2011 by Kat Arney

This entry is part 6 of 12 in our High-impact science series

Professor Walter Bodmer, along with his colleague Professor Ellen Solomon, helped to locate the APC gene in the 1980s

In this next post in our High-Impact Science series, we take a look at how our scientists in the late 80s laid the foundations for the discovery of an important bowel cancer gene called APC - now known to be faulty in around eight out of ten cases of the disease.

Publishing their research in two back-to-back papers in the journal Nature (here and here), the scientists – led by Professors Walter Bodmer and Ellen Solomon – tracked down the location of APC, paving the way for its eventual identification in 1991.

Thanks to the discovery, members of unfortunate families in which many cases of bowel cancer occur – often at a young age – can now be offered life-saving genetic tests and screening.

Studying APC and related genes has also led scientists to uncover the role of other important molecules that are involved in several types of cancer. This painstaking research is helping us to understand how cancer develops at a molecular level, laying the foundations for the development of future treatments.

Let’s look in a bit more detail at this landmark discovery, and what it means for bowel cancer patients and their families.

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EGFR – Wanna be starting something?

Posted on August 5, 2011 by Safia Danovi

This entry is part 5 of 12 in our High-impact science series

Dr Julian Downward’s work in the 1980s paved the way for several targeted cancer treatments used today.

For many, the 1980s represent social unrest and wardrobe disasters. But amidst the strikes and the legwarmers, the 1980s gave us much to be thankful for. For cancer scientists, it was a Renaissance period – a decade during which cancer research came of age and (unlike many of us) got a proper haircut.

Cancer Research UK was at the heart of this maturation, so as part of our High-Impact Science series, we thought we’d go back and revisit a discovery that not only spawned a whole new field of cancer research, but led directly to the development of drugs that are used to treat cancer patients today.

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