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Dr Serena Nik Zainal wins the Joseph Steiner Cancer Research Prize, 2019

last modified Oct 16, 2019 10:53 AM

Congratulations to Dr Serena Nik Zainal at the Unit for being named as the winner of the 2019 Joseph Steiner Cancer Research Award for her holistic work in the field of cancer genome interpretation and steering this knowledge towards clinical applications.





'Fingerprint database' could help to identify new cancer culprits

last modified Jul 09, 2019 02:28 PM

Somatic mutations in cancer cells, arising through cell-intrinsic and exogenous processes, mark the genome with distinctive  patterns termed mutational signatures. In a collaboration with David Phillips, King’s College London, Serena Nik Zainal’s group systematically explored mutational signatures associated with environmental agents that are either known or suspected to be linked to cancer.

In all, 79 agents from 13 families were used to treat human induced pluripotent stem cells (IPSCs), including agents found in everyday exposures like exhaust fumes, tobacco smoke, chemical dyes and things we ingest. A highly standardised set-up was used to ensure that all results were comparable to one another. Cell viability was aimed for 40-60%, functional DNA damage response assays were obtained, and metabolic activation was taken into consideration.

 Single-cell subclones were derived from recovered cells. In all, 324 iPSC subclones were whole genome sequenced to seek genome-wide mutation patterns. Computational analysis highlighted pathognomonic “fingerprints” of 41 environmental agents including 41 substitution patterns, 6 double-substitution and 8 indel signatures. New mechanistic insights was gained into mutagenesis and learned about contributions of DNA repair pathways to the final mutational outcome. Critically, these results will serve as a reference set of mutational signatures with public health and surveillance implications. In the future, when all tumours are sequenced, these reference catalogues of mutational signatures can be used to understand whether environmental mutagens are culprits in the development of a patient’s tumour.


The study entitled A Compendium of Mutational Signatures of Environmental Agents has been published in Cell  on 02 May, 2019.

It has received wide press coverage including in newspapers like the Guardian and the Telegraph and has also been widely discussed across social media channels and highlighted on various scientific and University websites. A video summary of the article released by Cell Press is available here:



New ways of looking at Kidney Cancer

last modified May 02, 2019 05:02 PM

Clear cell renal cell carcinoma (ccRCC), the most common subtype of kidney cancer, is characterised by biallelic inactivation of von Hippel Lindau tumour suppressor gene (VHL), mTORC1 signalling pathway activation and accumulation of cytoplasmic lipid. Inhibitors against receptor tyrosine kinases (e.g. VEGFR and PDGFR) and the mTORC1 complex are the current clinically approved therapies for ccRCC. Nevertheless, the overall objective response rates especially for advanced ccRCC remain low, with 5-year survival at less than 10%.Nature Communications logo

A recent study by Syafruddin et al. from Sakari Vanharanta's group, published this month in Nature Communications, elucidates previously uncharacterised molecular mechanisms underlying ccRCC pathogenesis. The new results show that a cellular signalling network centred around Kruppel-like factor 6 (KLF6), a super enhancer-associated zinc finger transcription factor, promotes ccRCC growth by supporting lipid metabolism and mTORC1 activity. KLF6 activates mTORC1 through the expression of the secreted factor PDGFB, a ligand for the PDGFR receptor. Thus, these results reveal a molecular link between two approved kidney cancer therapeutic targets, PDGFR and mTORC1. The new results also highlight the links between super enhancer-driven transcriptional networks and the activity of essential metabolic pathways. Detailed understanding of such links could pave the way for novel therapeutic intervention strategies.


The study entitled A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma by Syafruddin et al. has been published in Nature Communications on 11 March 2019.




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.



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.





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.


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.




Cellular identity theft leads to cancer metastasis

last modified Jun 07, 2018 02:14 PM

The spread of cancers to distant organs, or metastasis, is responsible for the majority of cancer-related deaths. How cancers develop the capability to spread has remained mostly unclear, however. New research led by Dr. Sakari Vanharanta at the Unit, University of Cambridge, has now identified molecular mechanisms that allow cancer cells to acquire characteristics from other cell types, such as white blood cells, in order to spread and form metastasis.

 Each cell in our body carries the same genes. Yet, due to differences in the ways cells read their DNA, and consequently express their genes, tissues behave differently. Gene expression is orchestrated by tissue-specific networks of gene regulatory elements called transcriptional enhancers, i.e. DNA sequences that control when and where specific genes should be expressed. Enhancers are therefore critical determinants of cellular identity. The new work, published in Cancer Discovery, sheds light on how cancer cells read DNA in unique ways, leading to vastly different behaviours, such as variability in metastatic potential. The work demonstrates how some cancer cells are able co-opt tissue-specific enhancers from unrelated cell types in order to activate genes that support metastatic progression. Through inappropriate enhancer activation cancer cells thus ‘steal’ features from normal cells, consequently facilitating metastatic spread.

 The new observations provide fundamental insight into a long-standing biological and clinical problem of metastasis, and they suggest that therapeutic approaches that would limit the capability of cancer cells to aberrantly activate enhancers could inhibit metastasis in patients.


The study entitled NF-κB–Dependent Lymphoid Enhancer Co-option Promotes Renal Carcinoma Metastasis by Rodrigues et al. has been published in Cancer Discovery on 6 June, 2018.

The article has also been covered as a feature by New Scientist and on the MRC website.




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.



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!



A new role for the breast cancer gene BRCA2 - safeguarding genes during transcription

last modified Jan 25, 2018 10:40 PM

Inheritance of a mutated copy of the breast cancer gene BRCA2 predisposes families to cancers of the breast, ovary, pancreas or prostate at an early age.  Despite intensive effort from scientists worldwide, how faults in BRCA2 cause cancer susceptibility is not well understood. Most available information suggests that BRCA2 is involved in homologous recombination to repair double strand breaks in DNA, which occurs each time that a cell divides. This DNA repair function is lost in cells with mutant BRCA2, causing DNA mutations to accumulate across the genome, and triggering early-onset of cancer.

 Now evidence has emerged that this is not the only way that mutation of BRCA2 leads to cancer. New research, recently published in the journal Cell Reports, by a research team led by Professor Ashok Venkitaraman at the MRC Cancer Unit has unexpectedly found that BRCA2 safeguards the expression of genes located throughout the human genome, preventing their breakage during the transcription process that precedes the synthesis of new proteins essential for normal cellular function. The research team has found that BRCA2 safeguards the transcription of DNA into RNA, by coupling to the molecular machinery involved in transcription, and ensuring that it smoothly moves across genes. In cells with mutant BRCA2, the transcription machinery gets held up as its starts, the proximal pause sites, causing accumulation of RNA-DNA duplexes which in turn leads to an increase in double strand breaks and genomic instability and ultimately results in cancer.

 These findings not only point to a surprising new way in which the inheritance of mutant BRCA2 may predispose to cancer, but also promises the future development of new treatments that target other proteins associated with the transcription machinery that may allow BRCA2 mutant cancer cells to survive.


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.



50 Movers and Shakers in BioBusiness, 2017

last modified Nov 14, 2017 05:10 PM

BioBeat - a collaborative effort between the Francis Crick Institute, the Cambridge Judge Business School’s cytosponge with scalebarEntrepreneurship Centre, and the Innovation Forum - recently released their 50 Movers and Shakers in BioBusiness 2017  report. One of the report’s five key themes was “Great Science”, in which ten women scientists were recognised as making significant scientific contributions. Professor Rebecca Fitzgerald was recognised for her work on the cytosponge as one of the ten. The significant contributions from her lab's research into the early detection of Barretts Oesophagus were also recently highlighted in a number of national newspapers following the CRUK's NCRI conference. These included:



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.






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.


Cambridge MP, Daniel Zeichner visits the MRC CU

last modified Jun 04, 2018 12:33 PM

The MRC Cancer Unit  recently hosted a visit by the Cambridge MP, Daniel Zeichner. In response to the Units invitation to local parliamentarians  as part of its celebrations of the MRC Festival of Medical Research, Mr Zeichner visited the Unit on the 14th of July. During his almost two hour long visit, the MP engaged in a very stimulating group discussion with all the Cancer Unit PIs about the importance and future of ongoing cancer  research focussed on ‘early’ detection, patient stratification and intervention, in keeping with the stated mission of the Unit. He was also taken on a tour across the research labs, where he interacted with students and post-doctoral researchers.

Daniel Zeichner, MP with teh MRC CU group leaders



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.



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.




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!



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 .


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.


Blocking the immune response to promote cancer progression: tumour lymph nodes as an accomplice to the crime?

last modified Aug 03, 2016 02:47 PM

Researchers from the Shields group at the MRC Cancer Unit have recently identified ways in which tumour-associated lymph nodes can change their behaviour following exposure to tumour-derived factors to exhibit features commonly associated with immune-suppression. Their study, entitled ‘Tumour-induced stromal reprogramming drives lymph node transformation’ was recently published in Nature Immunology.

Lymph nodes (LNs) function as a major immunological hub, which are essential for immune regulation and the generation of the appropriate immune response. However, lymph nodes are also the first site of spread for many types of cancer (that are not adequately ‘cleared’ by the immune system).

Tumour draining lymph node
A tumour draining lymph node showing T cells (magenta), B cells (red) and collagen networks of the stroma (blue). Proliferating cells are labelled in green.
It is becoming clear that LNs can generate a pro-tumour environment in response to tumour-  derived signals, but how these responses are formed and what drives them is yet to be  determined. The supporting stromal cell populations of lymph nodes are essential for their  maintenance and physiological function. While studies have demonstrated the impact of  tumour-derived factors on lymph node function (such as lymphangiogenesis), the contribution  of stromal cells such as fibroblasts (fibroblastic reticular cells, FRCs) and the associated network  they form has not been investigated.


This study is the first to demonstrate growth, structural remodelling and genetic (transcriptional) reprogramming of FRCS in tumour-draining lymph nodes (TDLNs) in response to tumour-derived factors even before tumour cells have spread. These alterations subsequently affected key immunological pathways, particularly decreases in guidance and survival cues, CCL21 and IL-7 respectively. This impacted not only the immune populations found within the LNs, but also their trafficking and localization once there. Combined, these have the potential to contribute to impaired function within these lymph nodes, promoting an immune-suppressive, pro-tumour environment.  

“These findings demonstrate that tumours have to capacity to remotely modify TDLNs through aberrant stromal signalling, which affects their structure and function” says Dr Jacqui Shields, lead author on this study. “This study significantly enhances our understanding of the mechanisms whereby tumour-associated lymph nodes support a failed anti-tumour immune response and ultimately tumour progression. We hope to take this forward to determine if stromal remodelling can be predictive of metastasis in patients who have not yet presented with secondary disease” 

Publication Details:

Riedel A, Shorthouse D, Haas L, Hall BA, Shields J. Tumor-induced stromal reprogramming drives lymph node transformation. Nat Immunol. 2016 Jul 11. doi: 10.1038/ni.3492. [Epub ahead of print]

Further information on research carried out by the Shields 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.



Allosteric Modulation of AURKA Kinase Activity via Disruption of its Protein-Protein Interaction with TPX2

last modified Jul 06, 2016 12:09 PM

The Venkitaraman group (in collaboration with researchers from the Department of Chemistry and Department of Biochemistry) have recently reported (in Scientific Reports) on the discovery of AurkinA, a novel inhibitor of AURKA (Aurora kinase A)-TPX2 interaction (Allosteric modulation of AURKA kinase activity by a small-molecule inhibitor of its protein-protein interaction with TPX2).

AURKA belongs to a family of Ser/Thr kinases, which are responsible for progression through mitotic cell division. It has been particularly implicated in many events surrounding transit through the G2 to M phases of the cell cycle and during mitotic cell division. Interaction with its protein partner, TPX2, promotes localisation to mircrotubules in the mitotic spindle and also modulates the catalytic activity of AURKA. Overexpression of AURKA is a common occurence in many cancer types, with efforts being made to therapeutically target its activity (using ATP-competitive inhibitors) in clinical trials. More recently, interest has shifted to allosteric inhibition of AURKA using compounds that interfere with interaction with TPX2.

This study demonstrated that AurkinA (the drug-like inhibitor of AURKA) disrupts the AURKA-TPX2 interaction and mislocalises the kinase from the mitotic spindle in cells. Unexpectedly, AurkinA binding to the Y-pocket (the pocket occupied by TPX2 in the AURKA-TPX2 complex) led to conformational alterations in AURKA that were distinct from those induced by TPX2 binding. These findings are thought to have implications for the chemical biology and selective therapeutic targeting of structurally related kinases.

Publication Details:

Janeček M, Rossmann M, Sharma P, Emery E, Huggins DJ, Stockwell S, Stokes JE, Tan YS, Almeida EG, Hardwick B, Narvaez AJ, Hyvönen M, Spring D, Grahame McKenzie G, Venkitaraman AR. Allosteric modulation of AURKA kinase activity by a small-molecule inhibitor of its protein-protein interaction with TPX2. Scientific Reports. 2016 Jun 24;6:28528. doi: 10.1038/srep28528.

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


An Insight into the MRC CU Open Day: MRC Festival of Medical Research

last modified Jun 11, 2018 10:45 AM

As part of the MRC Festival of Medical Research, the MRC Cancer Unit opened its doors to sixth-form students from a number of schools around Cambridge yesterday. Students were taken on tours of the Unit labs, where they completed a number of dry (computer-based) and wet lab-based activities based around the Units research. The lab tour was followed by a careers session, giving the students the unique opportunity to meet with staff from across the Unit.

The following video is a short extract of footage taken on the day. We hope this will give you some insight into the days events!




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.






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


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.


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!