Masarykova Univerzita partners present MErCuRIC at ECCB 2018 in Athens

Partners Dr Vlad Popovici and Anna Pečinková, Faculty of Informatics, Research Centre for Toxic Compounds in the Environment (RECETOX), Masarykova Univerzita presented MErCuRIC research, “Cross-platform gene expression signature for microsatellite instability in colon and gastric cancers” at the European Conference on Computational Biology (ECCB) 2018 in Athens, Greece. The conference was held September 8- 12, 2018.

ECCB is one of the main computational biology events in Europe. ECCB 2018 welcomed scientists working in a variety of disciplines, including bioinformatics, computational biology, biology, medicine, and systems biology. Participating in ECCB 2018 was an excellent opportunity to keep pace with cutting-edge research, and to network with members of the ECCB community.

View the Popovici/Pečinková presentation here.

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.

Abstract

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.

Abstract

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.

1st European Alliance for Personalised Medicine Congress

The 1st European Alliance for Personalised Medicine Congress – ‘Forward As One: Making personalised medicine a reality at national level’  is being held 27 – 30 Nov 2017 in Belfast, Northern Ireland.

The congress will be interactive, focusing on diseases, general science issues (Big Data, genomics, clinical trials, etc.) and the views, progress and health landscapes across Europe. With involvement from policymakers/regulators, MEPs, national healthcare officials, patient groups, HTA bodies, academics, researchers, healthcare professionals, industry representatives, journalists and more, the aim is to shape the EU health landscape now and into the future.

Registration is open and a preliminary agenda is now available.

EUPATI Webinar on Patient Experience in HTA | 26 September 2017, 17:00 to 18:30 CET

Join EUPATI‘s webinar to hear about patients relating their experience when going through Health Technology Assessment (HTA) processes. Two EUPATI Fellows, Paola Kruger (Italy) and Joan Jordan (Ireland) will share their experiences. The point of view of the pharmaceutical industry involved in the HTA process will also be highlighted. Two representatives from Roche, David McCarthy and Colm Fahey will participate in the discussion.

This is a great opportunity to join the discussion, share your perspective and ask questions in the Q&A sessions. Register here.

Prof. Bardelli Elected President of the EACR

Congratulations to Prof. Alberto Bardelli of UNITO on his election as President of the European Association for Cancer Research (EACR)!

You can read more here.

Bardelli EACR Aug 2016

MErCuRIC features in ECMC Annual Report

MErCuRIC has been featured as a case study in the 2014- 2015 Annual Report of the Experimental Cancer Medicine Centre (ECMC) Network in the UK.

ECMC 2015

New Related Publications Area

We’ve created a new area on the project website for publications from our partners that are relevant to MErCuRIC – check it out!

Rel Pubs

EUPATI Newsletter for Oct 2015

EUPATI, the European Patients’ Academy on Therapeutic Innovation has published their Oct 2015 newsletter – learn more about the experience of students who have just completed the first Patient Xpert Training Course and why regulatory agencies think patient education and engagement are important.

EUPATI Oct 2015