MErCuRIC presented at the 2018 All-Ireland Colorectal Cancer Conference, Dublin

MErCuRIC will feature in a presentation facilitated by Dr Austin Duffy of the Mater Misericordiae Hospital, Dublin at the 2018 All Ireland Colorectal Cancer Conference. Dr Duffy’s talk is “Clinical Trials in Colorectal Cancer” will take place on Saturday, May 19th at the Gibson Hotel, Dublin, Ireland.

This 2-day conference assembles healthcare professionals with a faculty of national and international gastroenterology, medical oncology, pathology, radiation, surgical and scientific experts from Europe and North America. The meeting will provide participants with the opportunity to facilitate best practice by discussing and disseminating the latest trends and developments in treatment and therapy of colorectal cancers, whilst also affording the opportunity to network with medical and surgical peers.

See the complete programme here.

Margaret Grayson receives Iris Colvin Lifetime Achievement Award for Health

On April 21, 2018, valued MErCuRIC PPI team member Margaret Grayson received the Iris Colvin Lifetime Achievement Award for Health, presented by the Women’s Forum NI (Northern Ireland, UK) at Belfast City Hall. The award is bestowed in recognition of the lifetime achievement of a woman in service, dedication and commitment, and in this instance to health.

The aims of the award are to recognise the contribution of women to society, promote the role of women and strengthen links between organisations, acknowledge how a woman has been a role model and inspired others around her, mark outstanding achievement at a personal level through service to others, acknowledge passion, drive and energy in what a woman has done in her lifetime, highlight inspirational leadership, provide encouragement to other women, and show the commitment and dedication of a woman to aspects of life and citizenship outside her own family.

Ruth Boyd, Cancer Research UK Senior Nurse/NICTN Deputy Director of the Northern Ireland Cancer Trials Network comments, “Margaret is an extremely worthy recipient of this award, as we are all aware!”

The entire MErCuRIC partnership congratulate Margaret!




‘Trialling tailored treatments for colorectal cancer’: A European Commission Research & Innovation Success Story

MErCuRIC was featured as a Horizon 2020 Success Story on the European Commission’s Policies, information and services webpage on April 14, 2018. Below is an excerpt from the story.

“Made-to-measure treatments are becoming possible because of the growing understanding of the genetic and molecular nature of cancers and disease in general,” says Coordinator Sandra Van Schaeybroeck of Queen’s University Belfast. As well as offering welcome benefits to future colorectal cancer sufferers, MErCuRIC is an example of where medical treatment is heading.

“MERCURIC focuses on a particular sub-group of CRC patients. However, this ‘stratified’ approach beginning with a genetic and molecular profile of a patient can, and is, increasingly applied to many cancers and other disease groups.”

Read the entire story here.

MErCuRIC Europa-Research&Innovation

MErCuRIC study published in Molecular Cancer Therapeutics

The MErCuRIC study ‘The unfolded protein response: a novel therapeutic target for poor prognostic BRAF mutant colorectal cancer’ has been recently published in Molecular Cancer Therapeutics. The body of research by Nicholas Forsythe, Alaa Refaat, Arman Javadi, Hajrah Khawaja, Jessica-Anne Weir, Heba Emam, Wendy L Allen, Frank Burkamp, Vlad Popovici, Puthen V Jithesh, Claudio Isella, Melissa J LaBonte, Ian G Mills, Patrick G Johnston, and Sandra Van Schaeybroeck was accepted for publication on 16 February 2018.


BRAFV600E mutations occur in 10% of colorectal cancer (CRC) cases, are associated with poor survival and have limited responses to BRAF/MEK inhibition with or without EGFR inhibition. There is an unmet need to understand the biology of poor prognostic BRAFMT CRC. We have used differential gene expression and pathway analyses of untreated stage II and stage III BRAFMT (discovery set: n=31; validation set: n=26) CRC and an siRNA screen to characterize the biology underpinning the BRAFMT subgroup with poorest outcome. These analyses identified the unfolded protein response (UPR) as a novel and druggable pathway associated with the BRAFMT CRC subgroup with poorest outcome. We also found that oncogenic BRAF drives endoplasmic reticulum (ER) stress and unfolded protein response (UPR) pathway activation through MEK/ERK. Furthermore, inhibition of GRP78, the master regulator of the UPR, using siRNA or small molecule inhibition, resulted in acute ER stress and apoptosis, in particular in BRAFMT CRC cells. In addition, dual targeting of protein degradation using combined Carfilzomib (proteasome inhibitor) and ACY-1215 (HDAC6-selective inhibitor) treatment resulted in marked accumulation of protein aggregates, acute ER stress, apoptosis and therapeutic efficacy in BRAFMT in vitro and xenograft models. Mechanistically, we found that the apoptosis following combined Carfilzomib/ACY-1215 treatment is mediated through increased CHOP expression. Taken together, our findings indicate that oncogenic BRAF induces chronic ER stress and that inducers of acute ER stress could be a novel treatment strategy for poor prognostic BRAFMT CRC.


Read about the roles of the partner organizations within MErCuRIC here.

doi: 10.1158/1535-7163.MCT-17-0603. [Epub ahead of print]

Read the complete publication here.

Published 18 February 2018

MErCuRIC team from RECETOX, Masarykova Univerzita publish study results

‘A critical comparison of topology-based pathway analysis methods’ authored by the team of Dr Vlad Popovici at the Research Centre for Toxic Compounds in the Environment (RECETOX), Masarykova Univerzita has been recently published in PLoS One. The body of research by Ivana Ihnatova, Vlad Popovici and Eva Budinska appeared online on 25 January 2018.


One of the aims of high-throughput gene/protein profiling experiments is the identification of biological processes altered between two or more conditions. Pathway analysis is an umbrella term for a multitude of computational approaches used for this purpose. While in the beginning pathway analysis relied on enrichment-based approaches, a newer generation of methods is now available, exploiting pathway topologies in addition to gene/protein expression levels. However, little effort has been invested in their critical assessment with respect to their performance in different experimental setups. Here, we assessed the performance of seven representative methods identifying differentially expressed pathways between two groups of interest based on gene expression data with prior knowledge of pathway topologies: SPIA, PRS, CePa, TAPPA, TopologyGSA, Clipper and DEGraph. We performed a number of controlled experiments that investigated their sensitivity to sample and pathway size, threshold-based filtering of differentially expressed genes, ability to detect target pathways, ability to exploit the topological information and the sensitivity to different pre-processing strategies. We also verified type I error rates and described the influence of overexpression of single genes, gene sets and topological motifs of various sizes on the detection of a pathway as differentially expressed. The results of our experiments demonstrate a wide variability of the tested methods. We provide a set of recommendations for an informed selection of the proper method for a given data analysis task.

Read about the role of the Masarykova Univerzita within MErCuRIC here.

doi: 10.1371/journal.pone.0191154

Read the complete publication here.

Published 25 January 2018

NICTN | Celebrating a decade of advances in cancer research

The Northern Ireland Cancer Trials Network (NICTN) presented at an Open Day on 17 February 2018 hosted by the Centre for Cancer Research and Cell Biology (CCRCB) in Belfast, Northern Ireland, UK.

As part of the NI Science Festival, the public was welcomed to the CCRCB Open Day on Saturday, 17 February 2018. The event ‘Celebrating a decade of advances in cancer research in Belfast’, invited the public to drop in to hear about clinical trials, the NI Biobank and population-based cancer research, and to meet staff from the NICTN and members of the NI Cancer Research Consumer Forum (NICRCF). The NICRCF utilise public opportunities to raise awareness about the availability of clinical trials including MErCuRIC. There were lab tours and interactive activities for the whole family. Talks were facilitated by leading researchers who are translating science into clinical practice. See the full programme here. The Open Day was attended by over 300 people from the Belfast area.

EuropaColon features a MErCuRIC patient’s perspective and our clinical trial

Through networking and information sharing, MErCuRIC is building bridges with colorectal cancer, personalised medicine and other stakeholder initiatives.

Currently, MErCuRIC is featured on the EuropaColon website with our first patient perspective story written by Ed Goodall. Special thanks to Ed! To read the entire story, click here. In addition, please visit our new web page for patient and carers stories here.

Finally, read about our clinical trial on the EuropaColon web page too.


Reflections from EAPM 2017 where MErCuRIC PPI was Highlighted

The 1st European Alliance for Personalised Medicine (EAPM) Congress was held in Belfast in November 2017 where Margaret Grayson presented MErCuRIC’s mission and objectives with an emphasis of the Public and Patient Involvement (PPI) aspects of the project. Margaret, Chair, NI Cancer Research Consumer Forum commented, “The conference was a great opportunity for listening, talking, sharing and meeting researchers, politicians, regulators and other patient and public involvement representatives. The Congress highlighted the need for partnership and collaboration and showed the importance of MErCuRIC as a pan Europe study to benefit people diagnosed with bowel cancer. Among those I had the privilege to meet and share information about MErCuRIC with were Barbara and Mark Moss who are Patient Ambassadors. Barbara is a EuropaColon Board member and Chair of the EuropaColon Patient Advisory Group. The poster presentation session gave further time and opportunity to forge links with EuropaColon and other groups with patient initiatives, and to explain MErCuRIC as a study and describe the PPI input into the project’s design.”

Ruth Boyd remarked, ”Majella Woods, Margaret Grayson and I representing the NI Cancer Research Consumer Forum (NICRCF) were delighted to meet ECPC Director, Lydia Makaroff at the 1st EAPM Congress. The motto of the ECPC is ‘Nothing about us, without us!’ an ethos the NICRCF subscribe to too! Lydia Makaroff expertly chaired a conference session entitled ‘The Value of Innovation from the Cancer Patient Perspective.’ Lydia set the scene providing background to the ECPC and their paper on the ‘The Value of Innovation in Oncology.’ Other speakers covered topics such as access to innovation in the National Health Service (UK) (including enrolment to clinical trials), potential innovation in the UK bowel cancer screening programme, disparities across Europe in cancer care and outcomes, and the Data Lab in Scotland. This was a fascinating and thought-provoking agenda offering perspectives on innovation in diagnosis and treatment, equality of access to cancer care, and the significance of data, but the session also offered hope for future cancer outcomes through policy, technological advances, and collective working across all stakeholders.”

Pictured below left to right at EAPM Congress 2017: (left photo) Margaret Grayson with Barbara Moss of EuropaColon and Mark Moss, a Patient Ambassador, and (right photo) Lydia Makaroff ECPC Director, with Majella Woods, Margaret Grayson and Ruth Boyd of the NICRC Forum.


EuropaColon Patients’ Survey on The Unmet Needs of Patients Living with Metastatic Colorectal Cancer

Bowel cancer/CRC patients: Please contribute to an important survey that will help EuropaColon understand how patients cope with a diagnosis of metastatic colorectal cancer. EuropaColon aims to unite patients, caregivers, healthcare professionals, politicians, the media and the public in the fight against digestive cancers. The Organisation works with 43 groups in 32 European countries and has been recognised as the voice of colorectal cancer patients in Europe.


‘Answers to the survey questions will help support you and other patients more effectively in the future.’

Healthcare in Europe is different in every country. You might live in a country where a healthcare team supports you from diagnosis onward, and you might have access to the latest treatments and medicines for cancer as well as support from the different services. Even so, your experience is important to us because regretfully in some countries patients are not so fortunate.

EuropaColon needs your input and will use your anonymous replies to make recommendations for change: ‘There are no wrong answers – it is all about your experience and that is what EuropaColon seeks to know. Without this information, health ministries will not listen to our arguments.’

This is the first time a survey like this has been commissioned in Europe for colorectal cancer. In order to make this information valuable, EurpoaColon needs to recruit 1000 patients across Europe and aims to get responses from100 patients per country. Please share this information widely!

The survey is available in 14 European languages. Find it here.

MErCuRIC team from the Università degli Studi di Torino publish in Nature

‘Inactivation of DNA repair triggers neoantigen generation and impairs tumour growth’ by authors Giovanni GermanoSimona LambaGiuseppe RospoLudovic BaraultAlessandro MagrìFederica MaioneMariangela RussoGiovanni CrisafulliAlice BartoliniGiulia LerdaGiulia SiravegnaBenedetta MussolinRoberta FrapolliMonica MontoneFederica MoranoFilippo de BraudNabil Amirouchene-AngelozziSilvia MarsoniMaurizio D’IncalciArmando OrlandiEnrico GiraudoAndrea Sartore-BianchiSalvatore SienaFilippo PietrantonioFederica Di Nicolantonio & Alberto Bardelli was published in Nature and online 29 November 2017.


Abstract: Molecular alterations in genes involved in DNA mismatch repair (MMR) promote cancer initiation and foster tumour progression1. Cancers deficient in MMR frequently show favourable prognosis and indolent progression2. The functional basis of the clinical outcome of patients with tumours that are deficient in MMR is not clear. Here we genetically inactivate MutL homologue 1 (MLH1) in colorectal, breast and pancreatic mouse cancer cells. The growth of MMR-deficient cells was comparable to their proficient counterparts in vitro and on transplantation in immunocompromised mice. By contrast, MMR-deficient cancer cells grew poorly when transplanted in syngeneic mice. The inactivation of MMR increased the mutational burden and led to dynamic mutational profiles, which resulted in the persistent renewal of neoantigens in vitro and in vivo, whereas MMR-proficient cells exhibited stable mutational load and neoantigen profiles over time. Immune surveillance improved when cancer cells, in which MLH1 had been inactivated, accumulated neoantigens for several generations. When restricted to a clonal population, the dynamic generation of neoantigens driven by MMR further increased immune surveillance. Inactivation of MMR, driven by acquired resistance to the clinical agent temozolomide, increased mutational load, promoted continuous renewal of neoantigens in human colorectal cancers and triggered immune surveillance in mouse models. These results suggest that targeting DNA repair processes can increase the burden of neoantigens in tumour cells; this has the potential to be exploited in therapeutic approaches.


Read about the role of the Universita degli Studi di Tornino in MErCuRIC here.

doi: 10.1038/nature24673

Read the complete publication here.

Published 29 November 2017