There remains an urgent need for new, effective therapies for mesothelioma.
Personalised medicine holds promise, however there are currently a dearth of robust, predictive biomarkers. Cancers including mesothelioma, are dynamic evolving systems. Recent advances in the genomic characterisation of mesothelioma using single biopsies has revealed the extent of population genomic heterogeneity. However, the extent of intratumour genomic heterogeneity (ITH) remains underexplored, in particular the hierarchical ordering of mutations that can be classified as early, spatially ubiquitous, versus later subclonal mutations that emerge during evolution. To identify gene targets relevant to the whole cancer, and minimize the risks of early sub-clonal resistance, understanding the phylogenetic architecture of mesothelioma is crucial.
sptial and temporal heterogeneity of these mutations. Intra tumour ITH underpins poor survival and drug resistance in cancer, by fuelling subclonal expansion under selection pressure exerted by drug treatments. Understanding the nature of ITH mesothelioma, will allow define a new hierarchy of genetic vulnerabilities, to underpin the discovery of new treatments most likely to target the whole cancer. In addition, this will allow the inference of mechanisms that underpin the formation, and natural history of mesothelioma. In order to advance treatment discovery, MEDUSA will therefore employ a second generation sequencing methodology (m-WES) with the goal of uncovering new, relevant drug targets to support synthetic lethal drug discovery, and accelerate development of new medicines to effectively treat mesothelioma.