Oncology is at the frontline of personalised medicine, moving beyond the previous model of administering cancer therapeutics based on trials of largely unselected patients beyond a simple phenotypic marker, to leading the way in utilising the molecular profile of an individual’s cancer genome to optimise their disease management . Tumours exhibit extensive heterogeneity, both between and within tumours, driving phenotypic variation and posing a significant challenge to personalised cancer medicine . The promise of utilising disease-specific biomarkers is having a tremendous impact on cancer medicine. In the United States, there are now more than 90 companion diagnostics and more than 500 clinically relevant biomarkers in drug labels . At the initial stages of the IPMT CoE two types of cancer will be targeted with the possibility of extending the focus at later stages. These targets will be (i) lung cancer, which has a high prevalence, extremely multifactorial and the number one cause of death amongst cancers, and (ii) primary brain tumours which are the most aggressive, amongst human malignancies. These cancers have been chosen both to assure maximum impact but also to serve as learning facilitators out of which technologies applicable to many other types of malignancies will emerge.
The promise offered by precision medicine and targeted therapies, with their reduced side effects, is of particular significance for the treatment of lung cancer patients. Despite tremendous advances in early diagnosis and therapy, cancer caused 8.2 million deaths worldwide in 2012 . Lung cancer is the lethal of cancers, with a disappointing 16.8% five year survival rate after diagnosis . This is despite a major change in the paradigm of lung cancer therapy which has shifted from the histopathology-based diagnosis to applications of molecular pathology, based on the identification of actionable drug targets. One of the important landmarks in this paradigm shift is the discovery of tumour driver mutations, exemplified by mutations in the Epidermal Growth Factor Receptor (EGFR), most of which are amenable to small molecule inhibitor therapies such as the Tyrosine Kinase Inhibitors (TKIs). Indeed it has been shown, in clinical trials, that patients with driver mutations who received the corresponding drugs had a prolonged progress-free survival compared to those with a driver mutation who did not receive the drugs and those without driver mutations . In Cyprus there are about 250-300 new cases of lung cancer every year and all patients, following first line conventional treatments of chemotherapy and radiotherapy, also benefit from targeted therapies. However as is the experience in other countries, most patients that receive targeted therapies develop resistance a phenomenon that requires multidisciplinary collaborative initiatives in order to be addressed.
Another possible target for precision medicine is the group of malignant gliomas, the most common primary brain tumours epitomizing the complexity of human multifactorial malignancies. The overall outcome of interactions among various biological functions underlying the malignant process is challenging or even impossible to predict. Glioblastoma Multiforme (GBM), the most aggressive glioma, is by far the most frequent type with a 2-year overall survival of only 25%. Despite the fact that the incidence of malignant gliomas defines a rare disease (15,000-18,000 yearly incidence in EU), the annual growth rate of the overall glioma market is increasing dramatically (17.4%). However, despite the emerging flurry of molecular and immunologic therapies, GBM patients have not as yet benefited. This poor prognosis is greatly attributed to (i) the large genetic and phenotypic spatiotemporal heterogeneity, (ii) the lack of successful delivery of therapies, either molecular or cell-based, across the Blood-Brain-Tumour Barrier (BBTB) and the brain tumour microenvironment, including the extracellular matrix (ECM) and (iii) the insufficiency of measures for the direct evaluation of the effectiveness of targeted therapies. Bridging medicine, biology and technology, this proposal brings high promise for an integrated solution for malignant gliomas, via multi-faceted targeted breakthroughs based on the concept of Precision Medicine.
Precision Engineering solutions through the realisation of IPMT have the potential to offer time-dependent detection and quantification of tumour parameters, including real–time monitoring of spatiotemporal distribution of druggable biomarkers. A substantial evolution of concepts is breaking the grounds set by the Key Enabling Technologies (KET) with a precision calibre proposed by the IPMT CoE, comprising (i) personalized smart devices, (ii) smart wearable and implantable systems, combining precision engineering and electronic/photonic assembly and (iii) smart surgical devices for augmented reality during surgical procedures, providing breakthrough and lasting solutions to a high impact societal challenge.In this context through this teaming project a major effort will be invested in using omics technologies and transomic approaches, to advance our understanding on the molecular mechanisms underpinning resistance in aggressive types of cancer such as lung and glioblastoma.