2011’s ‘top 10’ international developments (and our links to them)

Last week we wrote about the fantastic progress our researchers have made over the last 12 months.

But of course, many of their discoveries wouldn’t have been possible without the wider efforts of the international research community. Indeed, as someone once said, any individual scientist’s work ‘stands on the shoulders of giants’, and wouldn’t have been possible without the work of those that have gone before them.

Equally, scientists often work closely with colleagues in other labs – often in other countries – sharing resources, passing on expertise, and looking at the problem through multiple lenses.

Collaboration and sharing are, truly, the life-blood of science.

It was with this in mind that we reflected on an article on the Medscape website called ”2011 – top game changers in oncology”. The article lists what, in the opinion of a number of leading cancer researchers, were the year’s top ten developments in international cancer research.

We were pleased to see that, just as our own researchers’ progress is interwoven with the efforts of others, so many of these worldwide discoveries are built on previous hard work by scientists whom, thanks to your support, we’ve been privileged to fund.

In fact, of these top discoveries, Cancer Research UK’s researchers are there, clearly visible in the background, in six of them.

Here’s a list of Medscape’s top ten ‘game changers’, and – where relevant – our role to help bring them about.

10. European trial improves neuroblastoma outcomes

At June’s American Society of Clinical Oncologists (ASCO) conference in the US, researchers from Austria showed that a treatment strategy involving two drugs – melphalan and busulphan – in place of current standard chemotherapy, could dramatically improve survival rates for children with neuroblastoma.

As we blogged at the time, both of these drugs were developed by Cancer Research UK scientists back in the 1950s. One of the questions we get asked most frequently on our Facebook page is about progress in childhood brain cancers – this research shows how beating this form of the disease has been a burning issue for researchers past and present.

9. New horizons in lung cancer

Also at ASCO this year, the team behind a large US study of lung cancer genetics showed how a slew of previously-known mutations is involved in ‘driving’ the disease. Since drugs that target many of these are already being developed, this raises the prospect of a transformation in lung cancer treatment in the near future.

We’ve been heavily involved in the hunt for cancer-causing gene mutations over the years, and several of the genes spotted in this study were originally linked to cancer by Cancer Research UK-funded researchers – notably BRAF, EGFR and NRAS.

8. Big strides in ‘ER-positive’ breast cancer

A large US trial showed that a combination of a targeted treatment called everolimus and a second drug called exemestane was so effective in treating oestrogen-sensitive breast cancer that the trial had to be stopped early to allow all participants to receive the treatment.

The lead investigator said the results were the “strongest data ever”, while another commented that it was “the most important advance” since trastuzumab (Herceptin) for women with this subtype of breast cancer.

Exemestane is a drug that’s been around for a while, and works by blocking the action of aromatase – part of the machinery the body uses to make oestrogen. Our researchers led the first clinical trial of an aromatase blocker, and this was proof-of-concept that aromatase was an effective target for treatment.  We’ve also been heavily involved in trials to demonstrate how best to use these drugs.

7. Longer treatment of GIST with imatinib improves survival

A Finnish trial showed that patients with gastrointestinal stromal tumours (GIST) – a form of stomach cancer – survived even longer if they were treated with imatinib (Glivec) for three years rather than just one, settling a long-running debate in the medical community.

Our involvement here is substantial: in the early 2000s, researchers at The Institute of Cancer Research, funded by Cancer Research UK, worked in collaboration with others on the continent to run phase I, II and III clinical trials which resulted in approval of imatinib for use in advanced GIST. These results were used to convince NICE to recommend the drug on the NHS.

6. New drug for lymphoma gets US approval

“Probably the hottest new drug out there” was how one clinician described a new treatment, known as brentuximab vedotin (Adcentris), for patients with either advanced treatment-resistant Hodgkin’s lymphoma or treatment-resistant anaplastic large-cell lymphoma.

The drug is made of two parts – a ‘cancer-seeking’ antibody which targets a protein found on these lymphomas called CD30, and a toxic ‘warhead’ called MMAE, which poisons the cancer cells’ interior. The results are an exciting proof-of-concept, as a US researcher told Medscape: “We now have demonstrated that you can take an antibody and link it strongly to a poison. It will get in the cells and kill them, without doing much damage to the rest of the body.”

The drug is not yet licensed in the UK, but its manufacturers have applied for a European license.

5. Drug combo extends survival in pancreatic cancer, but with increased side effects

Research published in the New England Journal of Medicine showed that a combination of four different chemo drugs, known as FOLFIRINOX, gave ‘best ever’ survival rates in patients with advanced pancreatic cancer.

But the combination wasn’t without its downsides – the treatment is much more aggressive than the standard treatment of gemcitabine (either alone or in combination with other drugs), so the authors only recommend treatment for younger patients (<76 years)

4. High-dose methotrexate for acute lympoblastic leukaemia (ALL)

A large phase III trial in the US, reported at the ASCO conference, showed that treating children with a high-dose of a drug called methotrexate, rather than starting at lower doses and increasing them, led to better survival rates among those at high risk of recurrence.

The study’s authors propose that this should be a new standard of care.

3. Swedish trial shows new ‘Herceptin-like’ drug improves survival in Her2 breast cancer that’s spread

A new modified version of trastuzumab (Herceptin), called trastuzumab emtansine (or T-DM1), gave improved results when compared against the standard treatment (trastuzumab given with separate chemotherapy) for women with advanced breast cancer, according to a Swedish trial presented at a leading European cancer conference.

The new drug works in a similar way to the lymphoma drug we described above – it uses trastuzumab to ‘lock on’ to breast cancers that contain the Her2 protein, but also has a toxic ‘warhead’ – emtansine – to improve its ability to kill cells.

The advantage this drug has over using trastuzumab with a separate chemo drug is that it’s much less toxic, so can be given for longer.

Cancer Research UK researchers were heavily involved in the basic biological studies that ultimately led to trastuzumab, which targets a protein called Her2. As we described in our High-Impact Science post,  in the 1980s a team of our researchers in London discovered that a protein called EGFR is involved in cancer, and suggested that targeting it might be a good way to treat cancer. Other researchers subsequently discovered EGFR’s ‘sister’ protein, Her2 (EGFR is also known as Her1).

2. Lung screening edges closer

Medscape’s number two development is, to us, a little controversial. As we reported on our news feed in August, a large US trial showed that screening heavy smokers with a technique called ‘spiral’ CT scanning, cut subsequent deaths from lung cancer by 20 per cent. This is a great result, but needs to be treated with caution – investigative surgery after having a positive result can be risky and invasive, so how exactly to use this technique to minimise these harms.

It’s worth pointing out that the link between smoking and cancer was identified in the 1950s here in the UK by Professors Richard Doll and Austin Bradford Hill. Professor Doll, together with Professor Richard Peto, went on to find out more about this link, and much of this work was supported by Cancer Research UK. Consequently, we now know that smoking causes one in four cancer deaths, and is the leading avoidable cause of cancer.

1.  Finally – progress in melanoma treatment

It’s no surprise that the top spot for ‘game-changing’ research went to research on melanoma. Several decades had past with little new to offer patients with the disease, but the Medscape authors describe the development of two new melanoma drugs – vemurafenib and ipilimumab – as “unprecedented”.

The first of these – vemurafenib – is one of a group of drugs called BRAF inhibitors, which target a molecule called BRAF.  These drugs wouldn’t have been possible without the pioneering work of our scientists, who in 2002 discovered that over half of melanomas (and a significant proportion of other cancers) are caused by faults in the BRAF gene.

As well as being potentially a big step forward, vemurafenib exemplifies many elements of the new direction of cancer treatment, built on molecular knowledge of cancer’s inner workings (something we devote about 40 per cent of our funding towards)

Ipilimumab is a bit different. It’s an antibody, which – in some people – causes their immune system to seek out and destroy melanoma cells in their body.

Whilst we were disappointed to see that the high cost of ipilimumab, and the fact that doctors can’t predict who will respond and who won’t – means that NICE don’t think they’ll be able to recommend it for routine use in the NHS, it’s among several other immunotherapy drugs that have shown promise in clinical trials.

It seems that after many years in the shadows, immunotherapy is finally entering the limelight.

In summary

This isn’t a definitive list – other significant hurdles were cleared this year too (for example, this one, and this one). But reading through the Medscape report, we were struck by several things:

• the breadth of tactics used to tackle cancer
• the number of different types of cancer where things are now rapidly moving forwards
• and the excitement that decades of research in the lab, unpicking cancer’s inner secrets, is now starting to yield improved treatments that can help patients.

It was also heartening to see how the international research community is pulling in the same direction, and humbling to see how the research we fund fits into this bigger picture.

But there’s a long way to go – for example, cancers adapt and become resistant rather quickly to many of these new drugs. We urgently need to work out how best to use them, and more laboratory studies to keep refining and honing our knowledge of what makes cancer tick.

2011 has been an exciting year of progress for researchers around the world, and we truly hope that, with your continued support, this pace of change continues to accelerate in 2012 and beyond.

Happy New Year everyone. See you in 2012.

Henry

• Read the original Medscape article for more links and background
• 2011 – our researchers’ progress