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The MRC Cancer Unit at the Cambridge University Science Festival, 2017

last modified Jun 11, 2018 10:45 AM

On a day filled with glorious sunshine what a fantastic celebration it was for the MRC CU to mark the last day of the Cambridge Science Festival, 2017! The event was hosted again this year at the CRUK CI building as a collaborative effort between members of the Cambridge Cancer Centre. The Unit had a great team of students, post-docs and staff who were joined by the Cambridge University society, CATS, to promote the Unit’s mission through all the 8 activity stands that were on display. In addition, there were 2 very well attended talks (150+ visitors) presented by members of the Unit, relating to the role of computational biology in cancer and the link between metabolism and cancer.  With 300 + visitors ranging from retired pensioners to primary school children, it was a day filled with the buzz of creativity. All the activities at the stands had been carefully designed in-house with months of thought and effort having gone into it. Be it the hands-on experience of a key-hole surgery model, anatomical models of disease, using raspberry pies fruits and ducks to illustrate cancer mutations in the genetic code, a bespoke cancer invasion maze or chromosomes models to understand the impact of genomic instability, there was something to meet everyone’s taste and curiosity.  It was also a great opportunity to show-case the breadth of MRC funded science in Cambridge through the well-received MRC Colouring Book–a joint creation between various MRC Units in Cambridge. Last, but not the least, the event allowed the Unit to highlight the upcoming MRC Festival of Medical Research through publicity leaflets distributed to all visitors. Overall, a fun filled day of creativity and science coming together!



The metabolic landscape of cancer .

last modified Nov 18, 2016 05:07 PM

A study led by the laboratory of Christian Frezza at the MRC Cancer Unit has identified the metabolic signature of human cancers. In their research Edoardo Gaude and Christian Frezza have investigated the expression of genes related to metabolic pathways in a large cohort of cancer samples from the Cancer Genome Atlas. The analysis, which was performed on more than 20 different tumour types and covered 8000 patients, revealed a series of metabolic pathways exploited by cancer to sustain their growth and proliferation. Among these pathways, they found that suppression of mitochondrial genes, was a key signature of patients with the worst clinical outcome. In the attempt to explain the link between decreased expression of mitochondrial genes and poor prognosis, they found a strong correlation between abundance of mitochondrial genes and that of genes related to the epithelial-to-mesenchymal transition, a gene signature of aggressive and metastatic tumours.    

Frezza Metabolic landscape of cancerConsistently, they showed that metastatic melanomas exhibit a striking suppression of mitochondrial genes, compared to the primary tumour. Besides identifying a novel strategy for cancer patient stratification based on metabolic genes, this work paved the way for the investigation of novel metabolic determinants of metastasis, one of the major causes of death in cancer patients.

Their study, entitled ‘Tissue-specific and convergent metabolic transformation of cancer correlates with metastatic potential and patient survival’ was recently published in Nature Communications



Publication Details:

Gaude E, Frezza C. Tissue-specific and convergent metabolic transformation of cancer correlates with metastatic potential and patient survival. Nat Commun. 2016 Oct 10;7:13041. doi: 10.1038/ncomms13041


Further information on research carried out by the Frezza group can be found here.


The First Annual MRC Festival of Medical Research

last modified Jun 11, 2018 10:45 AM

The first annual MRC Festival of Medical Research will run from June 18-26 2016. MRC-funded research establishments will be showcasing and discussing their work through events and activities planned at MRC-funded units, centres and institutes across the UK. Examples of some events include open days, public lectures/debates, activity days, workshops, interactive seminars and quizzes. 

The objectives of the MRC festival are to: 

  1. Engage the MRC community to increase understanding of the MRC's strategic aims and their own contribution to these
  2. Build trust in medical research by sharing MRC-funded research with audiences
  3. Increase awareness and understanding of the benefits of medical research to society

A complete list of MRC festival events can be found at this link.

MRC Festival Cambridge Events

A number of exciting events will be taking place around Cambridge to mark this festival. While some of these are by invitation, many are open to members of the public! A leaflet containing the full details of these events can be found here. For a list of events taking place around Cambridge please click here.

The MRC Cancer Unit will be hosting an Open Day for Sixth form school students. A number of local schools are scheduled to visit the Unit on June 22. The students will be taken on tours of the MRC Cancer Unit labs, where they will hear talks from our scientists and complete some hands-on activities based on the research techniques that we use on a regular basis. The tours will finish with a short Q and A careers session and the opportunity to meet with staff from across the MRC Cancer Unit.






Targeting the 'Achilles heel' of mutant KRAS driven cancers...

last modified Aug 10, 2017 09:10 PM

The KRAS oncogene is frequently activated by mutations in cancers (including 90% of pancreatic cancers and 30-40% of colorectal or lung cancers). However, it has proven extremely difficult to find new drugs that directly inhibit activated mutant KRAS.

Work from Professor Ashok Venkitaraman’s laboratory at the Unit reported in Narvaez et al. now uses an alternative strategy to kill cancer cells expressing mutant KRAS. These researchers have exploited an “Achilles heel” that occurs early in cancer progression when cancer cells expressing mutant KRAS experience difficulties in accurately completing mitotic cell division.

Narvaez et al. have created a new class of potential drugs – Poloppins – which inhibit a key regulator of mitotic cell division, the polo-like kinases (PLKs). Poloppins do not inhibit the catalytic active site of the PLKs, but instead, target the protein-protein interactions that enable PLKs to engage their cellular substrates. Poloppins exploit the mitotic difficulties inherent in mutant KRAS-expressing cancer cells to induce their death during mitosis.

Poloppins not only selectively kill cancer cells expressing mutant KRAS in two-dimensional culture, as well as in organoids that mimic tumours, but also reduce the growth of KRAS-expressing cancers in an in vivo model. Poloppins show enhanced activity when combined with drugs that inhibit the c-MET receptor, which are already used in cancer therapy. Interestingly, cancer cells appear less able to develop resistance to the effects of Poloppins than to conventional drugs that inhibit the catalytic active site of PLK1. Together, these features suggest that drugs belonging to the Poloppin class have future potential for the treatment of pancreatic, colorectal or lung cancers, alone or in combination with other agents.

The creation of Poloppins exemplifies how vulnerabilities that occur early during the development of cancer can be exploited for cancer therapy. Moreover, Poloppins work by targeting the protein-protein interactions of kinases, illustrating a new strategy for drug development that offers potential advantages over conventional drugs that directly inhibit the kinase catalytic site.






Stimulating Cell Packing to Understand Human Growth

last modified Dec 01, 2015 06:10 PM

July 2015

Dr. Ben Hall has recently had his work published in Biophysical Journal, entitled: ‘Emergent Stem Cell Homeostasis in the C. elegans Germline Is Revealed by Hybrid Modeling’. Some of this work was selected as a covering image for the journal (below). In the following report, Dr. Hall discusses the rendering of this colour image and his groups innovative work with computational models of Cancer Biology.   

Stem cells are fundamental building blocks for organ growth. They are cells that have not committed to doing a specific job and, therefore, can be directed by different signals to perform a wide range of tasks. The cover image shows the shapes of stem cells while they undergo the process of organ growth, in a computational model. The cells themselves are packed tightly, and so to reduce the amount of unused space in the organ they form a hexagonal arrangement. This isn’t unique to cells; if you pack oranges or balls on a shelf tightly you can see the same kind of packing. The type of packing reflects both the shape of the cells, and the amount of crowding in their environment.

newsletterOur simulations don’t generate these images automatically. When we want to analyse this type of system we take the raw data, typically in a text file, and use a specialized tool to view it as a 3D object. We did this using the tool VMD ( and rendering the cells as spheres. This is a very powerful way to show how the cells move and grow and is important for many types of analysis.

For this image we wanted to generate a different kind of visualization. We wanted an image that showed the cell packing unambiguously and more closely resembled the experimental microscopy data. To do this we performed a mathematical analysis—a Voronoi decomposition—to calculate the edges of the cells. For each cell we then rendered these faces as colored blue glass and drew in a small green sphere to show the center of the cell. This clearly shows how cells in the niche pack hexagonally, and the resulting image resembles the microscopy images much more closely. This makes direct comparison much simpler and can be used to validate the simulations.

Both the cover image and our article show what can be done using detailed computational models to understand organ growth. Although the work is focused on one specific system—the germline from the nematode C. elegans—both the model and the approach may have significant impacts beyond this system. The organ structure, a stem cell niche, is found commonly in many different systems, and just as tumors may grow in the C. elegans germline, mutations may cause human stem cell niches to develop into cancers. Similarly, our group at the MRC Cancer Unit, University of Cambridge, is looking to use the same methods and tools to model different pre-cancer and cancer systems. This includes studying detailed models of individual components and large biochemical networks in cells. The Fisher group at Microsoft Research and the Department of Biochemistry, Cambridge University, is using the same computational methods to model the molecular mechanisms underlying cancer (e.g., leukaemia, glioblastoma) as well as blood development.

For information on our research, visit  the  group’s website and blog For information on the Fisher group, view and recent press release related to their work on blood development

– Benjamin A. Hall, Nir Piterman, Alex Hajnal, Jasmin Fisher

Skin Cells Play ‘Dice Games’.

last modified Dec 08, 2015 12:23 PM
Skin Cells Play ‘Dice Games’.

In maintenance (balanced) mode, the odds are balanced between production and shedding. In repair (expanding) mode, the odds of producing dividing cells are nine-times higher. CLICK TO ENLARGE.

Movies of cell growth explain skin graft success and may help understand cancer.

December 2015

- Dr. Phil Jones is a joint faculty member of the MRC Cancer Unit along with the Sanger Institute. He is the senior author on a recently published Nature Cell Biology paper, which shows how skin cells can 'switch' between two growth modes to maintain or repair skin. The following extract is adapted from a press release issued by the Sanger Institute.- 

How to maintain healthy skin and heal wounds is an intricate problem. Maintaining the skin requires exactly the right number of cells to divide to replace those shed from the skin surface. Too many cell divisions can lead to cancer, whereas too few will result in ulcers. Wound healing needs a short burst of cell production to fill the gap in the skin. Latest research shows that all dividing skin cells can flip between two probability game modes and so have the potential to both maintain and heal skin, challenging the view that only rare stem cells matter.

Understanding the rules of the games not only explains how skin maintains itself and heals wounds, but also shows how skin grafts work and suggests how changes to the rules could lead to cancer.

Watching high definition movies of human skin cells dividing in real time showed they play two types of dice game, for maintenance or wound repair. In the maintenance game, the odds are balanced between production and shedding, with a 50:50 chance of a daughter cell going on to divide or stopping division and migrating to the skin surface. These probabilities keep the skin in balance.  However, cells next to a wound temporarily switch to the repair game, in which the odds of producing dividing cells are nine times higher, ensuring rapid healing. 

“This research demonstrates that dividing human skin cells can switch their behaviour between these two modes of maintenance or repair, challenging the longstanding view that skin renewal and healing relies on a special population of stem cells,” says Dr Phil Jones, senior group leader at the Wellcome Trust Sanger Institute and MRC Cancer Unit, University of Cambridge.

To carry out the investigation of skin turnover, researchers took live imaging movies of more than 3,000 human skin cells dividing in culture. The images showed that single cells expanded exponentially in repair mode until they had produced multi-layered sheets of cells, after which the behaviour switched to maintenance mode. However, this is only half the story.

“By scratching sheets of cells in the balanced mode and observing cells next to the scrape, we saw that they changed into wound healing mode until the scratch was closed again,” says Dr Joanna Fowler, an author of the paper from the Sanger Institute. “The cells could switch backwards and forwards between the two states as required, proving that the behaviours were reversible.”

Skin cells 4
Skin cells 'switch' from maintenance mode (pink) to repair mode (blue) in response to a wound.

Skin loss due to burns or ulcers that won’t heal can be fatal and skin graft surgery is used to replace burnt or damaged skin. Sheets of skin can be grown from very small skin patches in the laboratory, and this can save the lives of patients with serious burns.

“As plastic surgeons, we have been growing sheets of skin from burns patients to save lives for decades. A single skin cell can create a patch of one centimetre diameter or more, and many of these together can make a whole sheet. However until now we couldn’t explain how this worked,” says Dr Amit Roshan, first author and Cambridge Cancer Centre Clinical Research Fellow at MRC Cancer Unit, Cambridge. “This research explains how skin cell cultures expand, and could lead to further improvements in wound healing in the clinic.”

The cells appeared to sense when their neighbours were missing, flipping from maintenance to wound healing behaviour: once they were surrounded by cells again, they flipped back. Inhibiting a cell signalling protein ROCK2 kinase prevented cells in expanding mode flipping back into balanced mode, indicating that cell signalling was required to make the switch. In further corroboration of the two mode games, the investigators found differences in gene expression between wound healing and balanced populations of cells.

“These findings have great implications for understanding cancer, where cells have too many dividing daughters. Mutations could change the rules of the game and load the dice in favour of dividing cells, leading to cancer.” Says Dr Phil Jones, “The knowledge that all dividing skin cells are the same but can switch their behaviour will help us understand how DNA changes associated with cancer alter cell behaviour.”

Publication Details:

Human Keratinocytes have two interconvertible modes of Proliferation.  Nature Cell Biology.

This work was supported by the Wellcome Trust, Cambridge Cancer Centre, Medical Research Council, the NC3Rs (National Centre for the Replacement, Refinement and Reduction of Animals in Research) and Cancer Research UK (Programme grant C609/A17257).


RNA Processing and the Response to DNA Damage

last modified Feb 24, 2016 02:47 PM

24 February 2016

Emerging evidence suggests that RNA processing pathways play a surprisingly intimate role in the cellular response to DNA damage. A recently published review by Prof Ashok Venkitaraman and Dr Vihandha Wickramasinghe in Molecular Cell (RNA Processing and Genome Instability: Cause and Consequence) provides an overview of recent insights into how RNA processing pathways contribute to DNA damage recognition, signalling and repair, and also selectively influence the expression of genome-stabilizing proteins and resolve deleterious DNA/RNA hybrids (R-loops) formed during transcription and RNA processing.   

The significance of these pathways is highlighted by the growing evidence that faults in these regulatory connections may be associated with the genome instability implicated in many human diseases, including cancer. This knowledge (the mechanisms described in this review) will allow this research field to turn its attention to determine how disrupting these RNA processing pathways could promote carcinogenesis.

Publication Details:

Wickramasinghe VO and Venkitaraman AR. RNA Processing and Genome Stability: Cause and Consequence. Molecular Cell. 18 February 2016. 

Further information on research carried out in the Venkitaraman group can be found here.



Reporting from the Hutchison/MRC Research Centre Annual Retreat

last modified Jan 20, 2016 12:55 PM


The 2015 Hutchison/MRC Annual Retreat took place at the Granta Centre, Granta Park, in Great Abington in November. This retreat saw a slightly different approach being taken from previous years, with a dedicated poster session taking place at the Hutchison/MRC Research Centre on the afternoon before the retreat itself (an afternoon session on November 19th). Research centre staff and students alike were able to come along to this session, where they could enjoy some refreshements and view the posters presented in a relaxed setting. The session was very well attended and enjoyed by all.

Retreat poster session

Both the poster and oral competitions of the retreat were judged by members of the Hutchison/MRC Research Centre postgraduate and postdoctoral societies. 

The poster competition was won by Dr. Emma Kerr for her poster entitled: ‘KRasG12D copy number defines metabolic reprogramming and therapeutic suscepatibilities’

The runner-up prize was awarded to Callum Campbell for his poster entitled: ‘Understanding differential checkpoint responses to genetic lesions and their implications for oncogenesis: development and application of imaging tools’.



Retreat presentations

The main scientific sessions of the Annual Retreat took place the following day (November 20th), with presentations from both group leaders and postdoctoral researchers on a diverse range of ongoing research themes from around the building. Scientific sessions were chaired by members of the Hutchison/MRC Postdoc Society.

The award for best talk by a postdoctoral researcher was won by Dr. Hamza Chettouh for his talk entitled: ‘Early detection and risk stratification of patients with Barrett’s oesophagus using the CytospongeTMDr. David Shorthouse took the runner-up prize for his computational biology talk entitled: ‘Osmotic regulation and cancer: Insights through the computational microscope’.


Athena Swan logo


An additional non-scientific talk was given by PhD student, Maximilian Fries, who spoke about the Athena SWAN organisation (a UK-wide organisation aiming to increase gender equality and diversity in education and research) and how both staff and students can get involved with and benefit from this.


Congratulations to all the poster and oral prize-winners, with thanks also to the representatives of the Hutchison/MRC Research Centre postgraduate and postdoctoral societies who did such a great job in judging both the poster and oral competitions.


Professor Rebecca Fitzgerald awarded with the Jane Wardle Prevention and Early Diagnosis prize

last modified Nov 15, 2018 01:06 PM

Professor Rebecca Fitzgerald was awarded the prestigious Jane Wardle Prevention and Early Diagnosis prize, which recognises individuals who have produced world-leading research in the field of prevention and early detection of cancer. The prize was announced at the 2018 NCRI conference in Glasgow.





Professor Rebecca Fitzgerald of the MRC CU interviews for Radio 4s PM

last modified Jun 04, 2018 12:35 PM

On Monday the 13th March, Professor Rebecca Fitzgerald,  was interviewed by BBC Radio 4’s  flagship news programme, PM.  This interview with the renowned presenter Eddie Mair highlights research carried out in the Fitzgerald lab at the MRC CU over the past many years that has led to the fruition of the  early detection device - Cytosponge (‘Pill on a String’) - which is now in phase 3 clinical trials and may revolutionise early detection of Upper GI cancers.  This interview  is perhaps particularly timely given the recent series of interviews with the, sadly now deceased, journalist Steve Hewlett. Steve’s reflections about his journey, from diagnosis to his untimely death,  through Oesophageal Cancer were broadcast every week on the same program and became hugely popular  and highlighted the need for research into earlier detection of cancers – something that is reflected through Rebecca’s research in this instance and is exactly the mission of the MRC Cancer  Unit, overall .


Professor Joan Brugge, Harvard University, delivers the MRC Cancer Unit Annual Lecture, 2018

last modified Feb 16, 2018 01:30 PM

On 6 February, Joan Brugge, Professor of Cell Biology and Director of the Ludwig Centre at Harvard University delivered the MRC Cancer Unit's Annual Lecture. Speaking to a packed audience at the Clifford Albutt Lecture Theatre, Professor Brugge dwelled on several novel unconventional mechanisms of redox adaptation that enable cancer cells to survive oxidative stress.

Thanks to Professor Brugge for a stimulating afternoon of insights and discussions!



Professor Ashok Venkitaraman, Director of the MRC Cancer Unit named as the winner of the 2017 Basser Global Prize.

last modified Dec 01, 2017 01:10 PM

Professor Ashok Venkitaraman has been awarded the 2017 Basser Global Prize from the Basser Center for BRCA at the University of Pennsylvania, USA, in recognition of his contributions to the field of research into the genetics of breast cancer, particularly for his laboratories work in explaining how mutations in the breast cancer gene, BRCA2, predispose to cancer and how knowledge of its critical role in genome repair can be exploited to devise approaches for early intervention in cancers.

Each year the award recognizes a leading scientist who has conceptually advanced breast cancer gene, BRCA1/2-related research that has led to improvements in clinical care. Individuals with mutations in the BRCA1 and BRCA2 genes have an exceptionally high risk of breast or ovarian cancer. Currently, the most effective preventive strategy is surgical removal of the breasts and/or ovaries.

 “It is our privilege to recognize Dr. Venkitaraman for his inspiring accomplishments, which have significantly contributed to our understanding of how cancer is suppressed by genes such as BRCA2,” said Susan Domchek, MD, executive director of the Basser Center for BRCA and the Basser Professor of Medicine in Penn’s Abramson Cancer Center.

“His pioneering work has helped clarify the basic mechanisms that govern genome repair, replication, and segregation during cell division, as well as their roles in cancer formation and treatment.  This knowledge is making a difference for patients with BRCA1/2 mutations by giving them better options for targeted therapies and improved quality of life.”

The award presentation will be accompanied by Ashok’s keynote address at the annual Basser Center for BRCA Scientific Symposium on Tuesday, May 22, 2018. The Basser Global Prize provides $100,000 in unrestricted support of the winner's BRCA1/2-related research efforts, a Basser trophy, and $10,000 cash prize, which will be awarded at the symposium.

“It is an honour to be recognized in this way by the Basser Center, which is at the forefront of efforts to improve the outcome of patients who bear BRCA1/2 mutations,” Ashok has said. “The Basser Global Prize will greatly enhance my laboratory’s ability to pursue promising new research avenues.”

The Basser Center was established in 2012 through a $25 million gift from Penn alumni Mindy and Jon Gray in memory of Mindy Gray’s sister Faith Basser, who died of ovarian cancer at age 44. The Basser Global Prize was established and subsequently endowed by Shari Basser Potter and Leonard Potter.



Prof Rebecca Fitzgerald’s Team Awarded New Cancer Research UK Funding

last modified Jan 13, 2016 09:02 AM

12 January 2016

Prof Rebecca Fitzgerald and her team have been successful in obtaining funding from Cancer Research UK for two new projects for 2016, which will support essential further research into efforts to improve the detection and diagnosis of oesophageal cancer and related conditions. These projects include the BEST3 trial and phase II of the OCCAMS (Oesophageal Cancer Clinical and Molecular Stratification) collaboration.

BEST3 Trial 

Cytosponge (pill-on-a-string) device for early detection of oesophageal cancer.

Early detection of oesophageal cancer has been shown to improve patient outcome. However, most patients with heartburn (the primary risk factor) are not investigated. Hence most cases of oesophageal cancer present at an advanced stage.  The BEST3 trial will assess whether the newly-developed CytospongeTM test for patients with reflux symptoms will be effective in increasing the detection of Barrett’s oesophagus. In Barrett's oesophagus the cells that line the lower gullet (oesophagus) are abnormal. The main cause is long-standing reflux of acid from the stomach (heartburn). People with Barrett's oesophagus have an increased risk of developing oesophageal cancer. 

The CytospongeTM device will be trialed in GP practices using a cutting-edge cluster randomisation approach.  Eighty GP surgeries will be randomised to either treat patients with reflux symptoms in the usual way or to offer all patients the opportunity to have a CytospongeTM test. Four thousand patients will be recruited to the trial, which will take 3 years to complete.

It is hoped that this research will establish whether the CytospongeTM test offers earlier detection and an alternative approach to invasive endoscopy. This will build on the previous multi-site BEST1 and 2 trials, providing the final step before this test could be introduced into main-stream practice in the UK. The project will be implemented in partnership with the Cancer Prevention Trials Unit at the Queen Mary University of London, and the Cambridge Institute of Public Health at the University of Cambridge.


OCCAMS Collaboration

Five years of funding has been secured by Prof Fitzgerald and her team for the second phase of the OCCAMS (Oesophageal Cancer Clinical and Molecular Stratification) collaboration. OCCAMS is a research study bringing together a network of clinical specialist centres treating patients with oesophageal cancer in the UK. Large-scale collection of clinical data and tissue is being used to help to identify clinical, demographic and molecular factors in the progression of oesophageal adenocarcinoma. Insights from the study will inform future trials of novel diagnosis and treatment strategies.

OCCAMS forms part of international sequencing efforts to generate a comprehensive catalogue of genomic abnormalities of ICGC Consortiumcancer tumour types as part of the International Cancer Genome Consortium (ICGC).  In collaboration with Simon Tavare’s group at the CRUK Cambridge Institute at the University of Cambridge, the project works to maximise the efforts of academic organisations and NHS trusts across the UK working in oesophageal cancer research.



Prof Rebecca Fitzgerald and Upper GI Team win prestigious BMJ Award

last modified May 20, 2016 03:34 PM

Congratulations to Prof Rebecca Fitzgerald (MRC Cancer Unit) and her Upper GI team, who recently (5 May) received a Gastroenterology Team Award at the BMJ Awards 2016 (Cytosponge – find cancer early). The BMJ Awards are the UKs premier medical awards programme, recognising and celebrating the inspirational work done by doctors and their teams.

Competition for this year’s BMJ Awards, now in their eighth year, was very strong, with 320 entries.  A rigorous selection process included presentations by shortlisted teams to a panel of judges that featured patient representatives for the first time. In collaboration with colleagues at Cambridge University Hospitals NHS Trust, the team at the MRC Cancer Unit developed a simple diagnostic test for oesophageal cancer, called the CytospongeTM, which the patient swallows, thereby avoiding the need for endoscopy.

BMJ Team Awards 2016
Upper GI Team (left to right): Mrs Irene Debiram-Beecham (Research Nurse), Professor Rebecca Fitzgerald (Principal Investigator), Dr Pierre Lao-Sirieix, (Senior Scientist) and Dr Maria O'Donovan (Consultant Pathologist and Research Associate).
The biggest risk factor for cancer of the oesophagus is heartburn - acid reflux - but the vast majority of patients who go to their GPs with this complaint are not sent for endoscopy. The CytospongeTM is a simple pill-on-a-string, which is swallowed by the patient, remains in place for a few minutes for the gelatin-like coating to dissolve, and is then retrieved with only minor discomfort. The cells it has collected are tested for the presence of a protein, Trefoil factor 3 (TFF3), which is a marker for Barrett’s oesophagus, a common precursor of cancer. Once patients have been diagnosed with Barretts’, they can then undergo routine surveillance and preventative treatment. In a series of four studies, the CytospongeTM has proven itself suitable for use in primary care, accurate in diagnosing Barrett’s and acceptable to patients.


It has taken 10 years for this concept (CytospongeTM device and subsequent test) to be developed to clinical application, but it is now entering its final stages. The team are currently launching a final study in primary care (BEST3 trial) to ensure that the health economics add up. BEST3 will be a trial of over 9,000 patients, recruited across 176 GP surgeries spread throughout the UK. The surgeries will be randomised into two groups. One group will treat their patients with heartburn in the same way that they would usually. The other group will offer all their patients a CytospongeTM test to see whether they have Barrett's (a condition that can in some cases develop into cancer) as part of their clinical care. The trial will take three years to complete and should tell us whether this test is suitable for routine clinical use. Commenting on the trial, Prof Fitzgerald said: “Then we’ll take it to the National Institute for Health and Care Excellence and say, ‘Here it is.’” There is a risk that use of the test might generate such a need for follow-up that endoscopy departments would be flooded. “We’re aware of that, so now we’re working on going one step further”, Prof Fitzgerald says.

BEST3 will start recruitment in late summer. Members of the trial team will be available to talk about the trial for International Clinical Trials Day on Friday 20 May. There will be a stall promoting clinical trials, including the opportunity to take part in a mock 'chocolate trial' on the main concourse at Addenbrooke’s Hospital from 11.30-14.00.

- Photos used in the report are © Copyright Philippa Gedge Photography


Pill on a String can Detect Cancer Without Need for Biopsy

last modified Dec 03, 2015 10:24 AM

July 2015

- Dr. Rebecca Fitzgeralds Group have recently published a paper in Nature Genetics wherein they describe the heterogeneity of the clonal architecture in Barrett’s oesophagus and oesophageal adenocarcinoma. Their findings strengthen support for the molecular Cytosponge technique, which overcomes sampling bias and has the capacity to reflect the entire clonal architecture. A press release based on this work and the Cytosponge technique was recently published in the Telegraph and shown below.-


Cambridge University has developed a quick way of testing for gullet cancer using a tiny sponge on a string.



The pill on a string which dissolves into a sponge 
By Sarah Knapton, Science Editor
4:17PM BST 20 Jul 2015

A ‘pill on a string’ has been developed by the University of Cambridge to detect the early signs of gullet cancer without the need for a biopsy. The pill is swallowed and when the outer case dissolves it reveals a sponge which can then be pulled up the throat lining, collecting cells. Researchers say the tiny sponge is more effective at picking up cancer because it takes a swab of the whole throat and not just a small area that a biopsy would examine. Oesophageal cancer is often preceded by Barrett’s oesophagus, a condition in which cells within the lining of the oesophagus begin to change shape and can grow abnormally.



When the pill dissolves it turns into a sponge.

Between one and five people in every 100 with Barrett's oesophagus go on to develop oesophageal cancer in their life-time, a form of cancer that can be difficult to treat, particularly if not caught early enough. The new test can pick up the earlier condition which means treatment can start sooner. “The trouble with Barrett’s oesophagus is that it looks bland and might span over 10cm,” said Professor Rebecca Fitzgerald, at the Medical Research Council Cancer Research Unit at the University of Cambridge. “There is a great deal of variation amongst cells. Some might carry an important mutation, but many will not. If you’re taking a biopsy, this relies on your hitting the right spot. “Using the sponge appears to remove some of this game of chance.”

The team has taken samples from 73 cancer patients over three years so that they know exactly which mutations indicate that the disease is present. They found patterns of changes where one letter of DNA had been switched for another to provide a ‘fingerprint’ of cancer.
The researchers also discovered that there appeared to be a tipping point, where a patient would go from having lots of individual mutations, but no cancer, to a situation where large pieces of genetic information were being transferred between chromosomes. Co-author Dr Caryn Ross-Innes adds: “We know very little about how you go from pre-cancer to cancer – and this is particularly the case in oesophageal cancer. “Barrett’s oesophagus and the cancer share many mutations, but we are now a step closer to understanding which are the important mutations that tip the condition over into a potentially deadly form of cancer.” The research was funded by the Medical Research Council and Cancer Research UK.


Professor Rebecca Fitzgerald discusses the Cytosponge technology (video).


Other key articles of this work were published by the Daily Mail NewsweekGizmagCambridge News , and WebMD .

Organoid cultures – a new tool in the study of a deadly solid tumour with very poor prognosis

last modified Sep 21, 2018 11:24 AM

Models of cancer are needed to test drugs and understand how they develop. Few models exist for cancer of the gullet (oesophagus). This recent publication from the Fitzgerald lab, selected as an Editors' Highlight by Nature Communications for its Stem cell and Disease as well as Genomes and Epigenomes portals is a collaborative study between the Sanger Institute Nature Communications logo(Mathew Garnet) and the MRC Cancer Unit (Rebecca Fitzgerald) and is based on the establishment of a panel of organoid cultures derived from Oesophageal Adenocarcinoma. These 3D cultures were established from patients undergoing extensive molecular characterisation as part of the International Cancer Genome Consortium. The authors were able to show that these organoids faithfully recapitulated the morphological, functional and genetic features of tumours and the cultures yielded interesting data on tumour evolution and susceptibility to chemotherapy and molecularly targeted agents. This research provides the community with a powerful translational tool for this very poor prognosis disease.



Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics.

The study entitled Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics by Xiaodun Li et al. has been published in Nature Communications volume 9, Article number: 2983 (2018) on 30 July, 2018.




Novel Uses of Computational Modelling to understand the role of Membrane Transport in Cancer

last modified Nov 12, 2018 11:19 AM

Membrane transporters are proteins used to maintain the concentration gradients of various chemicals between the exterior and interior of a cell. The gradients of these chemicals are then generally used for processes like maintaining cell size (osmotic regulation), and are also signalling molecules for processes like cell migration and division.

Nature Communications logo

In their new publication in Nature Communications, researchers from Dr Ben Halls group show for the first time that alterations in the expression of these membrane transporters consistently occurs in all cancers. Going further, the researchers were able to construct a computational model of the key chemical gradients and transporters within a cell, and show precisely how changes in the expression of them can alter cancer cell behaviour. The research is a start at understanding how these proteins can be used as potential markers or drug targets in the future.


Exploring the role of stromal osmoregulation in cancer and disease using executable modelling 

The study entitled Exploring the role of stromal osmoregulation in cancer and disease using executable modelling by  David Shorthouse et al. has been published in Nature Communications volume 9, Article number: 3011 (2018) on 01 August, 2018.


Novel promising biomarkers for the diagnosis of oesophageal squamous cell carcinoma

last modified Apr 27, 2016 02:02 PM

New research carried out by the Fitzgerald group has identified two promising novel biomarkers for the early detection and treatment of oesophageal squamous cell carcinoma (OESCC). Oesophageal cancer (OC) is a disease with a poor prognosis. The 5-year survival rate for oesophageal cancer is less than 10% in developing countries, where more than 90% of these cancers as OESCC. There is therefore an urgent need to identify new biomarkers for OESCC, with the potential to enhance the accuracy of patient diagnosis for prevention and/or treatment. 

Prof Fitzgeralds group used a publicly available cDNA dataset to identify 800 genes, which had altered expression in OESCC, relative to normal oesophagus. Validations of initial findings were carried out using qPCR (gene expression) and immunohistochemistry (tissue protein expression). Twenty genes were found to be significantly overexpressed in OESCC, relative to normal epithelium. Of these, TNFAIP3 and CHN1 showed significantly altered tissue expression across the sequence to OESCC. 

This study therefore identified biomarkers (TNFAIP3 and CHN1) for oesophageal squamous dysplasia and OESCC. The next step would involve a clinical study to assess the efficacy of TNFAIP3 and CHN1 as diagnostic biomarkers for OESCC. These biomakers could also help in the identification of patients with moderate/severe dysplasia that would benefit from preventative treatments.


Publication Details:

Couch G, Redman J, Wernisch L, Newton R, Malhotra, Dawsey S, Lao-Sirieix P, Fitzgerald RC. The discovery and validation of biomarkers for the diagnosis of esophageal squamous dysplasia and squamous cell carcinoma. Cancer Prev Res. 12 April 2016. 

Further information on research carried out in the Fitzgerald group can be found here.


Novel potential approaches for treatment of cancers with KRAS mutations: time for reassessment?

last modified Jul 18, 2016 10:27 AM

A recently published paper from the Venkitaraman group has identified new potential avenues for the treatment of certain forms of cancer, which carry mutations affecting the KRAS gene.

Approximately 25% of all human cancers carry KRAS gene mutations. These include most pancreatic cancers, as well as many cancers of the lung and colon. It has recently been suggested that drugs that interfere with cell division (anti-mitotic drugs) selectively kill KRAS-mutant cancer cells. This idea is being tested in clinical trials.

Dr David Perera and Prof Ashok Venkitaraman have found that mutations in KRAS alone do not predict whether cancer cells will respond to anti-mitotic drugs. Instead, contrary to expectations, high expression of a second cancer-causing gene, c-MYC, cooperates with KRAS mutations to determine responsiveness. The study, entitled ‘Oncogenic KRAS triggers MAPK-dependent errors in mitosis and MYC-dependent sensitivity to anti-mitotic agents’ was recently published in Scientific Reports.

Dr David Perera, first author on this study, commented: "Our findings caution against the use of KRAS mutation alone as a biomarker predictive of response to anti-mitotic drugs such as paclitaxel, a drug which is currently used in the clinic for the treatment of several types of cancer. However, we suggest that high expression of a second cancer-causing gene, c-MYC, may cooperate with KRAS mutations to determine responsiveness.”

This study suggests that drugs targeting the cooperation between c-MYC and mutant KRAS could provide new approaches to treat pancreatic, lung or colon cancers. “Our study opens up new avenues to therapeutically target KRAS-mutant tumours and to stratify patients in ongoing clinical trials of anti-mitotic drugs.”

Publication Details:

Perera D and Venkitaraman AR. Oncogenic KRAS triggers MAPK-dependent errors in mitosis and MYC-dependent sensitivity to anti-mitotic agents. Sci Rep (2016). DOI: 10.1038/srep29741

Further information on research carried out by the Venkitaraman group can be found here.



New insights about wild-type p53 restoration across mutant landscapes and genotype specific sensitivity to Statins in Lung Cancers.

last modified Aug 10, 2017 09:12 PM

Lung cancer is the leading cause of cancer related death worldwide due to its high incidence rates and limited effectiveness of available therapies. Approximately half of lung adenocarcinomas, the most common type of lung cancer, harbor mutations in a gene called TP53 (p53). p53, also known as 'the guardian of the genome', is a key player in the body’s in built defence mechanism against the development of cancer. However, due to its prominent tumour suppressive role, p53 is very frequently inactivated in cancer through mutations, being the single most commonly mutated gene in human cancers. As a consequence, p53 is also one of the most appealing cancer therapy targets.

Therapeutic vulnerabilities of lung tumours with distinct p53 mutations
However, as mutant p53 proteins cannot currently be targeted in the clinic, alternative targeting strategies aimed at these tumours are required. To identify mutant p53-dependent therapeutic vulnerabilities in lung tumours, Dr Carla Martins and her colleagues, at the Unit studied the transcriptional, metabolic and cellular characteristics of lung tumour models harboring distinct p53 deficiencies, namely complete loss of p53 (Null); mutations that cause loss of p53 contact with DNA and mutations that alter the correct conformation of the protein. Their work reveals that lung tumours with distinct p53 deficiencies have both common and distinct therapeutic vulnerabilities, and some of these may potentially be exploited with available therapies. On the one hand, this study shows that p53 restoration therapy, which is currently under development, is equally effective in p53-null and mutant lung tumours, demonstrating the potential of this therapeutic approach even when p53 mutations are present. On the other hand, the authors found that each p53 deficiency drove unique gene expression signatures that can in turn lead to mutation-specific vulnerabilities. In particular, they found that tumours with p53 contact mutations were sensitive to treatment with the cholesterol lowering drug simvastatin, a type of Statin, but this sensitivity was not observed in the other two p53 deficient tumour cohorts. Importantly, the authors identified a similar p53-mutation type specific gene expression signature in human lung tumors. This raises the exciting possibility that these specific subsets of lung cancer patients may profit from statin repurposing as a cancer therapy.

The study entitled Lung tumors with distinct p53 mutations respond similarly to p53 targeted therapy but exhibit genotype-specific statin sensitivity has been published in Genes and Development on the 9th of August, 2017.

Further information on research carried out by the Martins group can be found here.


MRC Festival of Medical Research, 2017- Celebrations at the MRC CU

last modified Jun 11, 2018 10:44 AM

The MRC Festival of Research this year was celebrated across the country from 17- 25 June. The main aim of the festival was to (1) Engage the MRC community to increase understanding of the MRC's strategic aims and their own contribution to these (2) Build trust in medical research by sharing MRC-funded research with audiences (3) Increase awareness and understanding of the benefits of medical research to society.

As part of this, the MRC Cancer Unit decided to focus on engaging with young minds through an Open Day at the Unit itself and the inauguration of a rolling Schools Roadshow program to visit schools outside of Cambridge. Our aim was both to showcase the research that goes on at our Unit, with special emphasis on the importance of ‘early’ in all aspects of cancer research as well as to highlight how numerous career opportunities open up through undergraduate and post-graduate training in science, technology and research.

On a scorching summer’s day, we had about fifty sixth-form students visiting us from four different local schools (Hills Road, Long Road, Parkside Federation and The Perse). Small batches of students along with their teachers were taken on a tour of our research labs where they had a chance to interact with our students and staff members and the opportunity to try out some of the hands-on experiments that had been carefully designed for them. To finish off there was a careers session over cakes and juice with a chance to meet staff from across the spectrum (research group leaders to science support), students and post-docs and a bag full of MRC memorabilia to take home. In spite of the hectic and hot afternoon, all the enthusiastic young visitors and our Unit members alike had a great time. Here is a flavour of what it was like on the day.



The same was true of our inaugural visit to Comberton Village College on the 23rd of June where our researchers and our partner team from the Cambridge University Society, CATS, presented an eclectic mix of research and career stories. So well received was this short presentation, that the MRC CU have been requested to come back in the autumn and talk to the whole school! …Here is a glimpse of that afternoon.



MRC Cancer Unit Programme Leader Wins United European Gastroenterology (UEG) Research Prize

last modified Dec 01, 2015 06:12 PM

rcf 2014smCongratulations to our programme leader, Professor Rebecca Fitzgerald, who has been awarded this year's UEG Research Prize for her pioneering work on early detection methods for oesophageal cancer. The annual prize, worth €100,000, is awarded each year for excellence in basic science, translational, or clinical research, and researchers must also be able to demonstrate that their previous work has had an impact in its field and is recognised internationally. Rebecca's work was particularly noted for its "practical and innovative approach to important clinical problems, which maximizes the potential for successful application".

The Prize will will support a research project entitled: Combination of quantifiable genomic assays with a patient friendly non-endoscopic cell retrieval device called Cytosponge™ for management of patients with Barrett’s oesophagus. The aim of the project is to bring the biomarker research undertaken by the Fitzgerald group to routine clinical practice.

For more information visit the UEG website.

MRC Cancer Unit at the 22nd Cambridge Science Festival

last modified Apr 11, 2016 11:59 AM

The 22nd Cambridge Science Festival was hailed as the biggest and best event ever by the organizers! The MRC CU was out in force at the Biomedical Campus on the last day of the Festival on March 20. 

Recent years at the Cambridge Science Festival have seen a number of events being run on the Biomedical Campus (a move from a city centre location). While the MRC CU have previously staged talks/activities at the Clinical School, this year saw a change from this, with the CU working closely with colleagues from the Cambridge Cancer Centre (Department of Oncology and CRUK-CI) to present a series of talks and activities along the theme of 'Discover the world of cancer research'. The MRC CU ran six activities at the festival this year, which were based at the CRUK-CI.

Festival posters
Some of our display posters

A number of associated posters were made, explaining the work that we do at the Cancer Unit and providing some further information on the range of activities that we were running. A number of group leaders from the Unit also gave talks at the Festival. Prof Rebecca Fitzgerald gave a talk at Mill Lane on March 16 (Does a pill on a string hold the answer for earlier diagnosis of oesophageal cancer), while both Prof Ashok  Venkitaraman (Making new medicines for old diseases) and Dr Shamith Samarajiwa (Battling cancer with data science) presented at the series of talks that were organised for the CRUK-CI Lecture Theatre on March 20. There was a great turn-out for the talks on the day, with many of the sessions at capacity.


Venkitaraman group 2
Members of the Venkitaraman group ready for public engagement action!
There were a total of 18 volunteers from the Hutchison/MRC research centre at this year’s Festival. For many of us, this was our first time participating in the Festival, so it was a unique and exciting experience for all involved! A number of new activities were generated for this year's Festival, which proved to be very popular with the crowds! Volunteers from the Venkitaraman group developed a game based around the concept of designing a cancer medicine to attack cancer DNA. They designed a number of shapes, representing drug molecules, which were placed into a ‘lucky dip’ box. Visitors were then asked to select a molecule to see if it would be a good fit to target cancer DNA. The efficacy of the molecule was determined by the extent of DNA damage, which was represented by a series of cell-based images.





Antibody and cell-sorting game

Online antibody game

Members of the Shields and Vanharanta groups joined forces to develop and run a ‘Day in the life of a scientist’ activity. This involved a number of games revolving around commonly used laboratory techniques. These included an antibody generation and labelling game (labelling of tissue samples for microscopy) and a cell sorting activity (flow cytometry).





Computational activity
Computational activity in action
The two computational groups also joined forces (Hall group and Samarajiwa) to generate a pattern-searching activity, which demonstrated the role computers can play in detecting mutations in individual patients’ cancers. Paper codes were handed out to visitors to our activities (representing normal or mutant genes). Raspberry Pis (representing desktop sequencers) were then used to scan these codes to determine where each person’s code falls on a resulting graph (normal or mutant gene). This was used to demonstrate how computers can be used to determine genetic patterns of different cancer subtypes and how these patterns can be used to design personalised cancer therapies.

This activity was run alongside a ‘Bioinformatics Tombola’ activity, which was run by the Fitzgerald group. Each visitor to this activity was asked to select a coloured egg from the ‘tombola’ (representing a cancer cell), within which contained a short DNA sequence. Visitors were then asked to try and find this sequence within much larger sequence (a difficult task!). This was used to demonstrate the values of bioinformatics to find mutation patterns in the genomes of cancer patients. It also demonstrated how DNA sequencing technology can applied to characterise each patient’s cancer and to match patients to the right therapy for their type of cancer.



Invasion maze'Norman' and the Cytosponge activity

While many new activities were generated for this year’s Festival, some very popular and successful activities from previous festivals were brought out from storage and used once again! The invasion maze proved very popular with young and older children alike, who tried to make it through the maze in as quick a time as possible. It was a great way to demonstrate the importance of tumour cell invasion to early metastasis as well as the processes involved (with some help from our colourful poster!).

Many people in the Unit will also be familiar with ‘Norman’, a life-sized model of a human torso, which was developed over a number of years by the Fitzgerald group. In this model, the front is opened out to reveal the heart, lungs and gastrointestinal tract. This model was used to demonstrate some interesting biological processes to schools at the Schools Roadshow over many years. It has also proven very effective in demonstrating the how the Cytosponge™ (pill on a string) technology can be used to detect cancer at its earliest stages. Zarah Abdullahi presented this activity for the Fitzgerald group. She also brought along some slides of tissue representing healthy and diseased oesophageal tissue and used these to show visitors what these two tissue types look like under the microscope. 





Conical evaluation
Conical evaluation showing majority of visitors agreed that the experience enhanced their understanding of cancer research


This is the first year that we have run our talks and activities from CRUK-CI and it has proven to be very successful! Many of the talks were full on the day and all of our volunteers reported great interest from the visitors that took part in their activities! Indeed, CRUK-CI reported that the crowd was significantly bigger than previous years. This success is largely due to the great enthusiasm and support from all of our wonderful volunteers! Thanks to all those that generously gave of their time to participate; giving talks, designing activities and posters, setting up the stands before the event and helping out on the day itself!

We think this conical flask on the left sums up the success of the event quite nicely. We asked our visitors if the event had improved their understanding of cancer research. We were delighted to see a majority of yes (blue discs) responses. Looking forward to the next round of public engagement events coming up later on this year!









Metabolism 'Rewiring' can Lead to Aggressive Lung Cancer

last modified Feb 25, 2016 01:32 PM

Dr. Carla Martins is a group leader at the MRC Cancer Unit. She is the senior author on a recently published paper in Nature. In collaboration with other researchers at the MRC Cancer Unit, her group have provided the first in-vivo evidence of metabolic rewiring in the malignant progression of lung cancer. This study also demonstrates that mutant Kras lung tumours are not a single disease, but a heterogeneous group of two classes of tumours, with distinct metabolic profiles, prognosis and therapeutic susceptibility. This is the subject of the following press release, which was recently issued by the Medical Research Council. - 

24 February 2016

Metabolism rewiring logo

Scientists have discovered that lung cancers with extra copies of a cancer causing gene-defect ‘rewire’ their energy supply, helping them to survive and making them more likely to spread.

Researchers at the MRC Cancer Unit at the University of Cambridge studied lung cancers with mutations in their Kras genes, which are found in around 30 per cent of adenocarcinomas - the most common type of primary lung cancer. They found that the number of copies of Kras mutations had a profound impact on the disease, as those with extra copies undergo a change in their metabolism.

Lung cancer cells with extra copies of Kras mutations increase their uptake of glucose - the major energy source in the body - and show alterations in the way this sugar is processed. Changes in glucose metabolism are a well-known cancer trait but this study revealed that cells with extra copies of mutant Kras utilise glucose differently from those either with a single mutation or normal lungs.

This metabolic “rewiring” enables these cells to cope better with certain cellular stresses but also means that they have unique metabolic needs that can be exploited therapeutically. Since an increase in the number of copies of Kras mutations were associated with more aggressive tumour features, such as the ability to spread, the therapeutic implications of the study are particularly appealing.

Until now all lung cancers with faulty Kras genes have been seen as one form of the disease. Dr Carla Martins, the lead researcher based at the MRC Cancer Unit, said: “Our study shows that we have been wrong to view all lung cancers with Kras faults as one form of lung cancer. Recognising that they may comprise distinct disease groups can help us improve the way we diagnose and treat these cancers.

“This is something urgently needed for patients with this type of the disease as current treatments have limited success. We now need to build on this work by determining the prevalence of this metabolic rewiring in patients and find ways to exploit or prevent it.”


Publication Details:

The study is published in Nature. PMID - doi:10.1038/nature16967

Further information on research carried out in the Martins group can be found here.




In quest of new genomic biomarkers for the clinic in Esophageal Cancer

last modified Feb 08, 2019 03:59 PM

Only around 12% of patients survive oesophageal cancer for 10 years or more. This is partly due to late diagnosis, as symptoms often do not present until the cancer is advanced, and partly due to limited treatment options. Oesophageal Adenocarcinoma (EAC) is the main subtype of oesophageal cancer in the UK and is on the rise in western countries – mainly because of lifestyle factors.


A recent study by Frankell et al. from the Fitzgerald group, published this month in Nature Genetics, scans 551 Oesophageal Adenocarcinoma (EAC) samples alongside matched RNA sequencing data from 116 samples of this cohort to provides an exhaustive catalogue of mutations and copy number alterations that are selected for in EAC and could have clinically relevant impact on the prognosis of the disease.

Importantly the study reveals driver mutations for EAC in 99% of patients and that more than half of the mutations (mainly related to Receptor Tyrosine kinases and or Cell Cycle proteins) could be targeted by drugs currently in trials for other cancer types, such as the CDK4/6 inhibitors already approved for breast cancer. This research, could help stratify oesophageal cancer patients to give them more personalised therapies. This in turn could provide options not currently available to patients beyond standard chemotherapy, radiotherapy or surgery. This also means phase II/III clinical trials to treat oesophageal cancer could be feasible in one to two years.

Interestingly, women were found to have more KRAS mutations than men. These mutations are often seen in other cancer types, but are rarely found in oesophageal cancer. This could indicate a different sub-type of the disease in women and suggest they might have a different prognosis or need alternative treatment.


Biological pathways dysregulated by driver-gene mutation and/or CNVs in 551 cases


The study entitled The landscape of selection in 551 esophageal adenocarcinomas defines genomic biomarkers for the clinic by Alex Frankell et al. has been published in Nature Genetics  on 04 February, 2019.



Hutchison/MRC Research Centre Highly Commended at EAUC Green Gown Awards

last modified Dec 01, 2015 06:11 PM

Our building, the Hutchison/MRC Research Centre, was Highly Commended at this week's annual EAUC Green Gown Awards. Now in their 10th year, the Green Gown Awards recognise the exceptional sustainability initiatives being undertaken by universities and colleges across the UK. The Research Centre was a finalist in the Technical Innovation for Sustainability category, based on its use of demand ventiliation control (a first in the UK). This system, along with an improved environmental culture amongst all occupants of the building, has resulted in a significant reduction in gas and electricity consumption, resulting in both financial savings and reduced carbon emissions. We hope that this award facilitates the sharing of best practice with other research institutions.

For more information about the awards visit the EAUC Green Gown website.

For more information about green activities within the MRC Cancer Unit and Hutchison/MRC Research Centre visit our energy and environment pages.

How supporting cells of the tumour kill the killers

last modified Mar 19, 2018 05:12 PM

Cancers have developed numerous ways in which to prevent our defences, that is our immune system, from destroying a Nature Communications logotumour. Many immune populations are found within a tumour, but it is the T cells that can ultimately decide tumour fate, and thus tumours frequently suppress their function.

A tumour is much more complex than a collection of cancer cells with many other cell types needed – these cells support the tumour in numerous ways and are known as the stroma. One population of supporting stromal cells, the cancer associated fibroblast, is associated with poor patient survival. T cells are often found near cancer associated fibroblasts, raising the possibility that cancer associated fibroblasts may help the tumour by interfering with our immune system.

New research by the Shields group has shown that cancer associated fibroblasts are able to eat tumour cell debris and present the material to T cells entering the tumour. This presentation process would normally instruct T cells to proliferate and activate so they can destroy their targets. However, in the tumour, cancer associated fibroblasts present material along with a negative signal through molecules FASL and PDL-2, which instead tells T cells to die, and allows the tumour cells to continue growing.

The mechanisms identified show for the first time that cancer associated fibroblasts directly interact with T cells to mediate immune suppression within the tumour but also helps to explain why in why cancer associated fibroblasts are associated with poor survival.

The study entitled Cancer-associated fibroblasts induce antigen-specific deletion of CD8+ T Cells to protect tumour cells by Lakin et al. has been published in Nature Communications on 5 March, 2018.



How Metabolic Reprogramming in mitochondrial dysfunction underpins uncontrolled cell growth and migration in Cancer

last modified Feb 16, 2018 03:11 PM

Cancer cells reprogram their metabolism in order to support the high energetic demands that are a cost of uncontrolled Molecular Cell logogrowth. Amongst these metabolic changes, activation of glucose metabolism is chief. It is known that glucose is metabolised via glycolysis and then fully oxidised in the mitochondria. Research has now shown that mitochondria are impaired in several cancer types. However, to what extent mitochondrial dysfunction contributes to the tipping towards glycolysis remains unclear.

New research led by Dr Christian Frezza published in the journal Molecular Cell,  capitalises on a new cell based model of mitochondrial dysfunction to address this link. Researchers, for the first time, have shown that mitochondrial defects lead to a profound metabolic rewiring of glucose metabolism and activation of glycolysis.

They further go on to show that this crosstalk between dysregulated mitochondrial metabolism and glycolysis in fact impinges on another important cellular metabolite - Glutamine. Glutamine is the most abundant amino acid in human blood and it is widely used by cancer cells for their growth. Through their study the researchers illustrate how in  situations of mitochondrial damage the breakdown of glutamine is co-opted to replenish NADH, one of the most important cellular  messenger molecule for multiple energetic reactions, and how this is achieved by a pathway known as reductive carboxylation. This glutamine-dependent NADH supply is essential to drive the activation of glycolysis, which in turn can support cell migration – a defining hallmark of cancer.

This is the first time that a bridging molecule, glutamine, and a metabolic pathway has been identified that link the loss of mitochondrial function with a switch to using glucose for metabolic needs and an eventual progression to cancer. This evidence expands our understanding of the energetic reprogramming  associated with uncontrolled growth and cell migration and offers new opportunities for targeting cancers.

The study entitled NADH Shuttling Couples Cytosolic Reductive Carboxylation of Glutamine with Glycolysis in Cells with Mitochondrial Dysfunction by Gaude et al. has been published in Molecular Cell on the 15th of February, 2018.



How Aldehydes, a common class of chemicals, causes cancer by breaking down DNA repair mechanisms

last modified Jun 29, 2017 11:15 AM

Aldehydes are a class of chemicals made in our own bodies in small quantities but increasingly found everywhere in our environment – from car exhausts, smoke, building materials and furniture to cosmetics and shampoos. Exposure to these chemicals has been linked with cancer, but the reasons for the link remain unclear.

New research led by Professor Ashok Venkitaraman at the MRC Cancer Unit shows that exposure to aldehydes could promote cancer by breaking down the defense mechanisms that prevent mutations in our genes.

Researchers from the Venkitaraman laboratory found that aldehyde exposure effects even normal healthy cells, but people who already inherit a faulty copy of the breast cancer gene BRCA2 are particularly sensitive.  Families who inherit faulty BRCA2 are at risk of developing breast, ovarian, prostate and pancreatic cancer: exposure to aldehydes could increase their chances of developing these cancers.

Our body converts the alcohol that we drink into aldehydes. Over 500 million people from countries like Japan, China and Korea inherit a faulty gene that makes aldehydes accumulate excessively in their bodies after alcohol consumption, and could be particularly sensitive to the cancer-causing effect.

“This study shows how chemicals to which we are increasingly exposed in our day-to-day lives may increase the risk of diseases like cancer,” says Professor Venkitaraman. “It also helps to explain why ‘the faults in our stars’ – namely the faulty genes we are born with – could make some people particularly sensitive to the cancer-causing effects of these chemicals.

“An important implication of this work is that it may be aldehyde exposure that triggers cancer susceptibility in people who inherit one faulty copy of the BRCA2 gene. This may help us in future to prevent or treat cancer in such people.”

The study, widely reported in several newspapers and online scientific portals, was published in the journal Cell.




Epigenetic Discovery Suggests DNA Modifications More Diverse than Previously Thought.

last modified Dec 22, 2015 09:21 AM

Dr. Christian Frezza is a group leader at the MRC Cancer Unit. He is the co-author (along with Dr. Sofia Costa from the MRC-CU) on a recently published paper in Nature Structural and Molecular Biology. In collaboration with researchers at the Wellcome Trust-CRUK Gurdon Institute, they have demonstrated and characterised a new form of DNA modification, which could open up the field of epigenetics. This is the subject of the following press release, which was recently issued by the University of Cambridge. - 

21 December 2015

The world of epigenetics – where molecular ‘switches’ attached to DNA turn genes on and off – has just got bigger with the discovery by a team of scientists from the University of Cambridge of a new type of epigenetic modification. 

Epigenetic modifications 2
The World of Epigenetics: Molecular 'switches' attached to DNA can turn genes 'on' or 'off'.

Published today in the journal Nature Structural and Molecular Biology, the discovery suggests that many more DNA modifications than previously thought may exist in human, mouse and other vertebrates.

DNA is made up of four ‘bases’: molecules known as adenine, cytosine, guanine and thymine – the A, C, G and T letters. Strings of these letters form genes, which provide the code for essential proteins, and other regions of DNA, some of which can regulate these genes.

Epigenetics (epi - the Greek prefix meaning ‘on top of’) is the study of how genes are switched on or off. It is thought to be one explanation for how our environment and behaviour, such as our diet or smoking habit, can affect our DNA and how these changes may even be passed down to our children and grandchildren.

Epigenetics has so far focused mainly on studying proteins called histones that bind to DNA. Such histones can be modified, which can result in genes being switched on or of. In addition to histone modifications, genes are also known to be regulated by a form of epigenetic modification that directly affects one base of the DNA, namely the base C. More than 60 years ago, scientists discovered that C can be modified directly through a process known as methylation, whereby small molecules of carbon and hydrogen attach to this base and act like switches to turn genes on and off, or to ‘dim’ their activity. Around 75 million (one in ten) of the Cs in the human genome are methylated.

Now, researchers at the Wellcome Trust-Cancer Research UK Gurdon Institute and the Medical Research Council Cancer Unit at the University of Cambridge have identified and characterised a new form of direct modification – methylation of the base A – in several species, including frogs, mouse and humans.

Methylation of A appears to be far less common that C methylation, occurring on around 1,700 As in the genome, but is spread across the entire genome. However, it does not appear to occur on sections of our genes known as exons, which provide the code for proteins.

“These newly-discovered modifiers only seem to appear in low abundance across the genome, but that does not necessarily mean they are unimportant,” says Dr Magdalena Koziol from the Gurdon Institute. “At the moment, we don’t know exactly what they actually do, but it could be that even in small numbers they have a big impact on our DNA, gene regulation and ultimately human health.”

More than two years ago, Dr Koziol made the discovery while studying modifications of RNA. There are 66 known RNA modifications in the cells of complex organisms. Using an antibody that identifies a specific RNA modification, Dr Koziol looked to see if the analogous modification was also present on DNA, and discovered that this was indeed the case. Researchers at the MRC Cancer Unit then confirmed that this modification was to DNA, rather than from any RNA contaminating the sample. 

“It’s possible that we struck lucky with this modifier,” says Dr Koziol, “but we believe it is more likely that there are many more modifications that directly regulate our DNA. This could open up the field of epigenetics.”

The research was funded by the Biotechnology and Biological Sciences Research Council, Human Frontier Science Program, Isaac Newton Trust, Wellcome Trust, Cancer Research UK and the Medical Research Council.

Publication Details:

Koziol, MJ et al. Identification of methylated deoxyadenosines in vertebrates reveals diversity in DNA modifications. Nature Structural and Molecular Biology; 21 Dec 2015

The text in this work is licensed under a Creative Commons Attribution 4.0 International License.  - See more at:

Christmas Lights credit: Anthony Quintano