We’ve moved!

After a lot of designing and developing, we’ve launched our new, modern and dynamic website. The new site will allow us to do what we have been trying to do with this blog over the past year and a half — opening a window on the ICR so that you can see what is happening inside one of the world’s leading cancer research institutes — but on a much bigger scale. You can read more about the new website and our plans for it in our blogpost on the topic, over at Science Talk‘s new home.

This means that it’s time to retire this WordPress site. Thanks to everyone for reading us so far, and please update your bookmarks and subscriptions so that you can continue to receive our latest posts at their new home. In a few weeks we will redirect this blog to the new site, but for now, here’s where you can find our new posts:

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How ‘big’ genetic screens are finding the answers to resistance to cancer treatments

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Targeted cancer treatments are starting to make a big difference to the lives of cancer patients, but their effectiveness diminishes over time and for some patients, these treatments may not work at all. Now large-scale screening techniques are helping scientists to uncover the mechanisms that help cancer resist treatment.


Here at The Institute of Cancer Research in London, we are pioneers in discovering and developing molecularly targeted treatments. These treatments work by attacking the mechanisms vital for the growth or survival of cancer cells and the development and progression of tumours.

Targeted treatments can be extremely effective, but cancer is a complex web of circuitry – flipping one switch might work for a while, but the disease has an uncanny knack of being able to rewire itself and acquire drug resistance.

But a process called RNA interference (RNAi) screening offers scientists a way of testing how this resistance develops.

RNAi allows scientists to investigate the role of individual genes on cell behaviour. Dr Steven Whittaker is leader of the Molecular Drug Resistance Team at the ICR and he uses RNAi screening to investigate these mechanisms of resistance in melanoma and colorectal cancer.

The screening method he uses works by taking viruses and modifying them with a small piece of genetic material called short hairpin RNA (shRNA). The shRNA induces the virus to switch off a particular gene inside a cell’s DNA by destroying the messenger RNA molecules which translate a gene’s message into a protein.

Infecting cancer cells with the virus switches off the target gene, and by switching genes off one at a time, researchers can start to tease out the mechanisms underlying resistance to treatment.

So far so good, but there might be thousands of genes that could potentially influence resistance to treatment – to investigate these mechanisms in a systematic and unbiased way, and to speed up the screening process, more sophisticated methods are needed.

Now large-scale or even genome-wide RNAi screens are becoming routine, thanks to libraries of shRNAs which pool together many thousands of shRNA-modified viruses at once, allowing scientists to silence almost any gene at will.

In a study published in the journal Cancer Discovery, Dr Whittaker and a team from the Dana Farber Cancer Institute and the Broad Institute in the US used a library of 90,000 shRNAs targeting 16,000 genes in melanoma cells. They infected the cells with the viral library, then treated them with a targeted melanoma drug called a RAF inhibitor until treatment-resistant cells started to emerge.

Using next-generation sequencing, high-tech machines which can scan thousands of samples simultaneously, they measured the relative abundance of each shRNA found in the resistant cells compared to control samples, to see which genes were silenced in the resistant melanoma strain.

They found that the gene NF1, which encodes the tumour-suppressing gene neurofibromin, was the gene most frequently lost in treatment-resistant cells. The loss of NF1 resulted in resistance to RAF inhibitors by reactivating a pathway called MAPK, which is consistent with findings from other melanoma studies where RAF inhibition has stopped being an effective treatment.

To confirm losing NF1 was the reason why melanoma cells developed resistance, they infected another strain of melanoma with a virus to silence NF1 directly. When they added the RAF inhibitor, they found that NF1 suppression did indeed allow the melanoma cells to evade treatment. And importantly, NF1 mutations were found in melanoma patients who developed resistance to the RAF inhibitor.

Dr Whittaker’s study shows that large-scale RNAi screening is an effective way to investigate resistance mechanisms in cancer. The technique can identify the genes which allow cancer cells to develop resistance, and once the genes at work have been identified, researchers can start to develop methods to prevent resistance to treatment happening in the first place.

Patenting – not always black and white

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How big a role does business play in getting new diagnostics and treatments to patients?

A pretty important one, argues one of our leading experts on the commercialisation of healthcare in a new podcast exploring its impact in breast cancer research and care.

The podcast accompanies the latest in a series of public engagement events on breast cancer genetics which I attended earlier this month, organised by the Progress Educational Trust, a charity working on policy and public engagement around genetics and related areas.

An expert panel featured Dr Angela Kukula, who is the Director of Enterprise here at The Institute of Cancer Research in London, alongside people with a variety of other perspectives – a representative from the health insurance industry, a former breast cancer patient, and a lawyer specialising in biomedical intellectual property.

I went along to hear the panel discuss the impact of commercialisation on breast cancer research, treatment and management. Dr Kukula’s talk and the accompanying podcast focused on the key role that partnering with companies plays in taking the ICR’s research findings to patients. We have blogged about this before and you can read more here.

One of the topics that came up several times in the discussion was the role of patenting in cancer research, and Dr Kukula explained the ICR’s patenting and licencing policies – which seemed to surprise a few members of the audience. Some did not expect academic institutions like the ICR to hold patents for their intellectual property, but perhaps they began to appreciate that the issue of patenting is not as black and white as they had imagined.

Dr Kukula described the different approaches the ICR takes to patenting. She explained that for technologies where large investment is needed from a company to take the product to patients – such as a potential new drug – we would usually file a patent, since otherwise a company might not be prepared to invest in their development.

The debate got really interesting though when we hit on the topic of gene patenting. Some members of the audience seemed surprised that the ICR holds six patents that include genetic sequences, and Dr Kukula talked through just why this was necessary to preserve – rather than constrain – academic freedom.

She explained that the ICR and other not-for-profit organisations sometimes chose to file patents defensively to prevent commercial organisations from doing so – since these companies would otherwise retain for themselves the exclusive rights to gene sequences.

It is the ICR’s policy that maintaining exclusive rights to genes is likely to be detrimental to public health, so when we patent DNA sequences we aim to maximise patient benefit by making rights available on a non-exclusive basis to as many organisations as possible.

The rest of the discussion covered topics such as alternatives to patenting to protect IP, debate over who should have access to patient data and what they might want to use it for, and health and life insurance for cancer patients.

If you missed the event you can listen to the podcast featuring interviews with the speakers where they discuss the key messages that they planned to make during the debate. It’s worth a listen – it certainly introduced me to ideas that I hadn’t thought about before, and the event flagged up just how many misunderstandings there are when it comes to the role of business in healthcare.

The final event in the series will be held on Thursday, and looks at the facts, fiction and future of breast cancer risk – more details can be found here.

Could circulating tumour cells be the swiss army knife of cancer markers?

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Circulating tumour cells exist in tiny numbers in the blood of cancer patients, but they could be one of the best ways to track a patient’s disease, and they could also help researchers to develop new treatments.

Circulating Tumour Cells from prostate cancer

Circulating tumour cells

Here at The Institute of Cancer Research in London, our scientists investigate cancer from all angles to discover new ways to diagnose, monitor and treat the disease. Our discoveries have led to innovative targeted treatments like the prostate cancer drug abiraterone, and we blogged recently about how we’re using the cold sore virus to kill cancer cells.

But once cancer has metastasised to other parts of the body in most cases it becomes extremely difficult to treat. Metastasis is the primary cause of death of patients with cancer – causing over 90% of cancer deaths.

Still, there is now increasing interest in using the cells cast off by tumours when they spread as a multi-purpose tool for cancer – the swiss army knife of cancer markers, if you like. Assessing these cells could potentially help in everything from monitoring disease progression to directing treatment strategies and monitoring their effectiveness.

Professor Johann de Bono, Professor of Experimental Cancer Medicine at the ICR and an honorary consultant at The Royal Marsden NHS Foundation Trust, has just published an interesting review on the subject in the journal Clinical Cancer Research. He, along with colleagues at the ICR, and in Spain and Switzerland, discuss how circulating tumour cells – or CTCs – are becoming essential tools in cancer research.

CTCs that have been shed by tumours into a patient’s bloodstream are the first signs that cancer may be spreading to other parts of the body. At these early stages there may be only one CTC for every 100 million cells in the blood – which makes accurately measuring CTCs a very difficult task.

But new technologies are now making this possible. Measuring CTC counts from blood samples can predict the seriousness of a patient’s cancer for several cancer types, including bowel, breast and prostate cancer. It can also assess if cancer treatments are producing an effect in patients, which could speed up the development of new therapies.

In a recent phase III prostate cancer trial carried out in the UK by Professor de Bono, researchers measured CTC counts from prostate cancer patients taken at multiple times during treatment with the drug abiraterone.

They found that when CTC levels dropped to under five for every 7.5ml of blood measured, there was a noticeable improvement in patient survival, which was seen from as early as four weeks after beginning treatment.

This is useful because at the moment, clinical trials must run for years to determine the effects of drugs on patients’ long-term survival, and CTCs could potentially provide the same sort of information much more quickly.

But the newest and most exciting application of CTCs is their use as molecular markers of a patient’s cancer.

CTCs as molecular markers

CTCs have the same genetic material as the tumour they came from, which means they share the same mutations driving tumour formation and growth. Analysing CTCs can tell scientists about the genetic make-up of cancer, without the need for invasive procedures like biopsies.

Molecularly characterising CTCs can tell us how treatments change antigens found on the cell membranes of CTCs, or how they reduce populations of CTCs with specific genetic markers. By measuring how CTCs change genetically before and after treatment regimens, researchers can see more clearly which molecular mechanisms are being affected by cancer treatments.

CTCs have already been used to test for a number of cancer-causing genes like HER2 and EGFR. Measuring changes in HER2 expression of CTCs from breast cancer patients could be an important way to detect disease recurrence or progression, while studies have shown that CTCs expressing EGFR can indicate the emergence of mutations leading to drug-resistance in lung cancer patients.

One day, we may be able to use CTCs to make treatment choices in the clinic, measuring the evolving characteristics of a patient’s tumour to select the most effective treatment at any given time.

But a word of caution about these promising, multi-purpose markers. Tumours are known to harbour populations of cells with distinct genetic mutations, so there are concerns that CTCs may not always represent the tumour as a whole or its more aggressive components.

Further research is needed, but as the technology becomes more sensitive and economical, measuring CTCs looks increasingly likely to become an essential tool for both cancer research and treatment.

Mapping the biodiversity of tumours

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Just as studying a single organism can’t tell you everything about the ecosystem it lives in, a single biopsy might not describe the diversity of cancer cells found within an individual tumour.

Cancer is often spoken about as a single disease, but there are more than 200 different types, and it is well known that the genetic characteristics of tumours vary substantially between patients.

What is also becoming clear is that cancer is a shape-shifting beast, and can vary genetically within a single tumour, and continually evolve during a course of treatment.

This variation – and the way advantageous genetic traits are selected for under a Darwinian process of evolution – appears to be a key reason why cancers are so difficult to treat.

Charles Darwin's sketch of an evolutionary tree [Public domain], via Wikimedia Commons

Charles Darwin explained the variation of different species through natural selection and evolution – it is becoming clear that the same processes can drive drug resistance in tumours

While information about the tumour biology can be obtained from a biopsy, a growing tumour produces cells with new mutations. Most of these mutations either have a neutral or negative effect on the cancer cells, but so-called ‘driver’ mutations might benefit the cancer. And just as a population of animals will evolve to better resist predators (by being faster or stronger), so cancer cells can evolve resistance to treatment.

I spoke to Dr Marco Gerlinger, a team leader in our new Centre for Evolution and Cancer at The Institute of Cancer Research in London, about his recent review of the research on the variation within tumours – intratumour heterogeneity – in kidney, prostate and bladder cancers.

“Researchers have known about intratumour heterogeneity for a while,” he told me.

“But next-generation sequencing has allowed us to look across the whole genome of specific cancer cells in order to gain a much more detailed insight into the genetic variation of these urological cancers.

“We saw considerable variation of driver mutations in cells from spatially separate regions of the same tumour. This is a problem, since single biopsies in these cancer types might not give enough information about the type of disease that that patient has.”

A biopsy might suggest the patient should respond to a particular treatment, when in fact other parts of the tumour could contain aggressive cancer cells that have the capacity to be drug resistant.

The authors suggest that multiple biopsies or new methods of imaging these urological cancers could provide a greater vantage point from which to survey the genomic landscape of a patient’s cancer.

With this vision of a population of cancer cells, clinicians could then target the first mutations to arise in a tumour – the so-called ‘truncal mutations’, which unlike more recent arrivals are likely to be present in every cancer cell. Such an approach could potentially circumvent the development of drug resistance.

Dr Gerlinger said that it is important to remember that a patient’s cancer is constantly changing and evolving. “We need to think carefully about the dynamic and evolutionary nature of cancers so that we can uncover the broad themes to drug resistance. For example, resistance in some cancers follows the same broad pathway – and this can be targeted with new drugs.

“There are plenty of examples in evolutionary biology where species could not adapt to changing environments and became extinct. In the longer term, we want to understand how drug therapies need to be designed in order to overwhelm the cancer’s ability to evolve.”

Researchers gather to discuss hottest topics in cancer research

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Today’s date has been ringed on our calendar for many months now as our researchers gather for the start of our annual conference.

This is a chance for researchers across all disciplines at The Institute of Cancer Research – from PhD student to division heads – to come together in a huge melting pot of knowledge, expertise and enthusiasm. They’ll be discussing some of the hottest topics in cancer research.

The two-day conference kicks off with a welcome presentation from our Academic Dean, Professor Clare Isacke. She has an infectious enthusiasm for science and the ICR’s role as an academic institution, and I’m sure our researchers will be inspired by her aspirations for the conference.

Over the next couple of days our researchers will share their latest research which explores some of the most topical scientific subjects at the ICR, including cancer evolution, the role of cell signalling networks, cancer imaging and the challenges faced by targeted therapy. The conference is closed, to give our researchers the chance to talk openly about very early data, but the results presented will be the big scientific papers of tomorrow.

We are making significant headway in genetics-based cancer research, but I am also looking forward to hearing about our cell-based research which focuses on the differences in behaviour between cancer cells and normal cells. These differences can be important targets for cancer therapies, as structural differences alone are sometimes too minor to be easily druggable.

Nothing at the ICR ever seems to stay still. So many new people, centres and buildings have sprung up in the last year and these will be an important focus for the conference. For example, our new Centre for Cancer Imaging, which brings together all our imaging capabilities into a new state-of-the-art building, is set to speed up the development of new imaging techniques for patients, and to use imaging to accelerate our drug discovery work. Researchers relocating to the new centre will discuss how they are combining different imaging techniques, such as MRI and ultrasound, to provide greater depth and breadth of information than use of a single imaging technique alone.

Another pioneering initiative is our Centre for Evolution and Cancer. Our researchers within the centre are exploring the evolutionary principles underpinning the development of cancer. They are trying to answer three of the biggest questions in cancer research: why are humans so vulnerable to cancer, what determines the protracted and unpredictable development of cancers in the body over years or decades, and why are we seeing drug resistance so frequently? Some of the centre’s researchers will be discussing their research to discover new approaches to cancer treatment that can avoid or combat drug resistance, by influencing the evolutionary trajectories of cancer, or reducing its ability to evolve adaptively.

The conference also provides an opportunity to hear from our up-and-coming researchers – our PhD students and clinical research fellows. Five have been selected to present their work, which covers a diverse range of topics including cell diversity in acute lymphoblastic leukaemia, cell signalling in pancreatic ductal adenocarcinoma, and cancer-causing mutations in childhood brain cancer. These bright minds will be the future of cancer research and I’m sure their presentations will be hugely insightful.

Finally, the conference will recognise the best scientific posters – those that demonstrate the quality of the science and presented with clarity to a professional audience, as well as the winner of our science writer competition. Our researchers need to be well versed in not only presenting their work to a technical audience, but also to the wider non-scientific community. The ICR’s Mel Greaves Science Writing Prize seeks to reward that ability. The winning piece will be posted on our website.

The ICR is part of a healthy future for medical research

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Dr Chris Lord at the APPG on Medical Research Summer Reception.  Photo credit: Wellcome Images

Dr Chris Lord at the APPG on Medical Research Summer Reception. Photo credit: Wellcome Images

We often hear the UK life sciences sector described as a vibrant ecosystem, bringing together government, charity and private sector funding. It’s a comment we’ve made ourselves before, and is widely seen as a real strength for UK science.

This week I was lucky enough to attend a Summer Reception at the House of Commons which really drove home the point – showcasing the results of these sorts of collaborations and the benefits of investing in medical research.

MPs, Peers, research funders, industry representatives and medical researchers gathered at the Summer Reception, organised by the All Party Parliamentary Group on Medical Research.

I attended the event with Dr Chris Lord, a team leader here at The Institute of Cancer Research, who works on breast cancer genetics and ways of exploiting specific genetic weaknesses of cancer cells.

He presented research conducted here at the ICR which has led to a new class of drugs called PARP inhibitors – which have gone on to show remarkable effectiveness in clinical trials of patients with breast, ovarian and prostate cancer.

Around 20 years ago, scientists at the ICR discovered the BRCA2 gene, which when mutated increases the risk of breast, ovarian and prostate cancer. This discovery of BRCA2 and its links to some cancers paved the way for genetic testing and the discovery of treatments for patients with the faulty gene.

ICR researchers went on to find that the protein produced by the BRCA2 gene plays a vital role in repairing damaged DNA, and found a way to turn this weakness against cancer cells.

Cells with BRCA mutations can survive as another DNA repair pathway exists, involving PARP proteins. But if cells do not have either a functional BRCA repair pathway or a PARP repair pathway, they die.

Scientists found that blocking PARP proteins killed cancer cells with BRCA mutations, but left normal cells – with a working BRCA repair system – unharmed. Cells with BRCA mutations were up to 1,000 times more sensitive to PARP inhibitors than normal cells. It was a completely new approach to cancer treatment.

This research underpinned the discovery of a new class of drugs called PARP inhibitors, which have now been successfully tested against many types of cancer in clinical trials. You can read more about this work in a booklet which accompanied the event – A Healthy Future for UK Medical Research.

The event coincided with the launch of a new report on the economic benefit of cancer research in the UK, which several of the speakers made reference to in their talks. Cancer Research UK covered the launch of the report on its blog which you can read here. The key message for me was that for every pound invested in cancer research, the UK economy gains 40p every year afterwards, providing economic return as well as health gains.

The work that Dr Lord presented at the Summer Reception is a great example of how an initial discovery – that of the BRCA2 predisposition gene – can have just this sort of impact. The discovery has enabled families with a history of breast cancer to be informed about their risk, guiding decisions over preventative measures and personalised cancer treatment, and laid the groundwork for developing novel forms of therapy for BRCA-associated cancers.

We think this work is a real British success story, showing how close interaction between ICR scientists, a UK drug company, NHS hospitals and funding bodies can improve the outlook for cancer patients.