MRN newsletter January 2018

The latest news from the mesothelioma research network

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BLF awards £474,949 to fund mesothelioma research

The BLF is delighted to announce the award of £474,949 to fund four high-quality mesothelioma research projects.

BLF mesothelioma project grant – Dr Zsuzsanna Tabi, Cardiff

Project title: Combination treatment modelling for the immunotherapy of mesothelioma

The team will develop a physiologically relevant ex vivo laboratory model to study whether targeting additional immunosuppressive and cancer pathways, known to be relevant in mesothelioma, would synergise with PD-1/PD-L1 inhibition.

BLF mesothelioma PhD studentship grant – Dr David Fairen-Jimenez, Cambridge

Project title: Genes in cages. Design of smart capsules for the delivery of macromolecules

Recently, metal-organic frameworks (MOFs) have been proposed for drug delivery. The project aims to use metal organic frameworks for drug delivery for mesothelioma, combining design and synthesis with in vitro & in vivo performance.

BLF mesothelioma pump-priming research grant – Dr Katherine Finegan, Manchester

Project title: Understanding how ERK5 signalling drives malignant mesothelioma progression

The aim of this project is to understand the mechanisms by which ERK5 regulates mesothelioma progression in vivo and to validate the utility of ERK5 inhibitors to treat mesothelioma.

MesoUK-BLF mesothelioma research grant – Dr Ed Hollox, Leicester

Project title: MEDUSA – Mesothelioma Evolution: Deciphering drUgable Somatic Alterations as potential targets for synthetic lethal therapy

This project will assess the phylogenetic architecture of mesothelioma in order to identify genetic weaknesses and new druggable targets.

The BLF announced its new grant round, including mesothelioma specific grants, in December 2017. The deadline for preliminary applications is 29 January 2018.


MRN researcher profiles

Dr Sarah Taylor, Post-Doctoral Research Associate

S taylor

Judy Coulson's Lab, Institute of Translational Medicine, University of Liverpool

My research investigates the relationship between BAP1 and malignant pleural mesothelioma (MPM). BAP1 is a deubiquitylase and tumour suppressor that can regulate protein stability and transcription. Loss of function mutations are observed in around 50% of MPM cases and germline BAP1 mutations are associated with a cancer predisposition syndrome. BAP1 has been a major focus of our lab for several years and previous BLF-funded work generated isogenic BAP1 mutant cell lines on which multi-omics analysis was performed to reveal BAP1 dependencies and potential vulnerabilities in drugable pathways. The overarching aim of my project is to determine whether BAP1 loss defines molecular sub-types of mesothelioma and whether these can predict sensitivity to particular treatment strategies.

I am utilising our isogenic cell panel together with a cohort of patient-derived mesothelioma cell lines and tissues from MesobanK, which have different histological-subtyping and BAP1-status, to assess the correlation of BAP1 with candidate drugable targets. For the most promising candidates, we are testing in cells whether drugs already in clinical use might be selectively re-purposed for the treatment of either BAP1-positive or BAP1-negative mesothelioma.

I chose this post-doc as my background is in cell signalling and cancer biology. However, I was particularly drawn to the translational element of this research. The outlook for mesothelioma patients is very poor, with current treatments having little to no beneficial effect. One of the strongest driving factors for me is that my research could ultimately contribute towards changing this.

I hope that my fundamental biology research will help the MRN research community to better understand the changes that occur at the molecular level in mesothelioma, such that it will seed ideas for new clinical trials and novel methods for stratifying patients to the most suitable treatments. Get in touch with Sarah about this profile by emailing S.E.Taylor@liverpool.ac.uk.

Dr Anna Bibby, NIHR Doctoral Research Fellow & Honorary Respiratory Physician

Bibby

Academic Respiratory Unit, Bristol Medical School, University of Bristol

ASSESS-meso (IRAS ID 220360) is the largest prospective, longitudinal, observational cohort study of mesothelioma patients in the UK. The study is open to all patients with mesothelioma, regardless of performance status or tumour location. Participants will be followed up from diagnosis until death, with regular collection of clinical data, radiological information, patient-reported symptom and quality of life scores, and biological sample storage. For more information see Mesothelioma UK’s website.

We are aiming to enrol 700 participants, from multiple UK sites, over a 10-year period. ASSESS-meso is currently open at North Bristol NHS Trust and Oxford University Hospitals NHS Trust, with another 5-10 centres planned to open over the next year.

As Principal Investigator, I wanted to set up ASSESS-meso for several reasons. Much of our current understanding of the UK mesothelioma landscape is informed by the National Lung Cancer Audit Report. This excellent publication provides a snapshot of mesothelioma practice around the country. However, it does not have the scope for longitudinal follow up, or collection of patient-reported outcomes. By collecting patient-centred clinical data over participants’ entire disease course, I hope ASSESS-meso will complement the Mesothelioma Report.

I also wanted to design a pragmatic study that produced results that reflected the whole mesothelioma population. The ever-expanding number of treatment trials underway in mesothelioma often, by necessity, have strict eligibility criteria. I designed ASSESS-meso to be an inclusive study, thus optimising generalisability and hopefully improving patients’ access to research.

Finally, we are using ASSESS-meso to evaluate an innovative trial methodology, called Trials within Cohorts (TwiCs). Using the TwiC design, ASSESS-meso could be used as a resource to identify and enrol eligible trial participants, thus improving recruitment efficiency. A feasibility trial is currently underway, and we await the results with excitement. Get more information about the trial by emailing nbn-tr.tilttrial@nhs.net


BLF survey on clinical trials

The BLF conducted a survey of people with mesothelioma to identify attitudes related to participation in clinical trials and any barriers faced. The survey was promoted by patient support groups and individual clinicians also encouraged patients to participate.

Most of the people who took part had pleural mesothelioma, and the age group most largely represented was 67–76 years of age. People from the north east and north west of England were most likely to answer the survey and there was high representation from coastal regions.

31% of the 72 people that told us about their participation in trials were currently in a clinical trial or had taken part in the past. When asked about future intentions, 78% of the 56 people that responded on this topic said they would take part in a clinical trial if deemed eligible to take part. Of the people that said they had asked a health care professional about taking part in trials, 56% of the people that responded about their experience, felt they got the information they needed to decide whether to take part in a trial.

In terms of the major barriers people felt they faced in relation to participating in trials, fear of being placed in a placebo arm of a trial, not knowing what trials are available and not being sure if they were eligible for trials were the most common barriers. The BLF will be working with its mesothelioma research network (MRN) and patient groups to develop more information about trial design and to better promote trials open to patients. For a copy of the full report email Cheryl via mrn@blf.org.uk


Pick of the papers

We keep an eye on the latest original research papers and the BLF research team handpicks three to showcase

Long-fiber carbon nanotubes replicate asbestos-induced mesothelioma with disruption of the tumor suppressor gene Cdkn2a (Ink4a/Arf) (PDF, 6.6MB)

This study addresses the long-standing question of which early molecular changes drive carcinogenesis during the latency period of mesothelioma development. It also suggests that carbon nanotubes may pose a similar health hazard to asbestos.

Determination of PD-L1 expression in effusions from mesothelioma by immuno-cytochemical staining

This research demonstrates malignant mesothelioma effusions are suitable for immune-cytochemical assessment of PD-L1 expression in malignant cells, and the results are similar to those reported for histological specimens.

High dose irradiation after pleurectomy/decortication or biopsy for pleural mesothelioma treatment

Treatment of intact lung with pleural intensity-modulated arc irradiation in patients with malignant pleural mesothelioma proved safe and feasible. Survival rates were encouraging for both biopsy-only and pleurectomy/decortication groups.


Good to know

We’ve pulled together some useful updates, relevant whether your research is basic or clinical.

Updated mesothelioma information

The British Lung Foundation has updated their mesothelioma patient information, which is available online. Healthcare professionals can order up to 80 hard copies for free via our professionals’ shop. Patients can order a free hard copy via our public shop.

NC3Rs launch new tool to plan animal research

The NC3Rs Experimental Design Assistant is a free online tool that helps researchers optimise the experimental design of research using animals and ensure that the number of animals used is consistent with the scientific objectives.

Five-minute read: Collaboration - just the latest buzzword in medical research?

Executive Director of Business Development at LifeArc, Mike Johnson, blogs about collaboration in research. He gives two great examples of recent commercial and academic partnerships that are driving research progress.