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'S-HERTOGENBOSCH, Netherlands

Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.2.4.1-8 | Award Amount: 7.82M | Year: 2011

Each year more than 63,000 new cases of kidney cancer are diagnosed in the European Union. Approx. 50% of all patients have metastasized renal cell cancer (mRCC) at presentation or develop metastases during follow-up. 5-year relative survival of mRCC has been extremely poor: between 5 and 10%. In the past few years, so-called targeted therapies that suppress angiogenesis have changed the clinical practice for patients with mRCC dramatically. Both response and toxicity to these expensive drugs is, however, extremely variable. With an increasing number of compounds becoming available, choice of compounds and sequence is becoming extraordinary challenging. Classical patient and tumor characteristics appear to have poor predictive ability. The aim of this project is to identify germline genetic markers that predict response and toxicity (by the use of high-resolution whole genome SNP arrays in groups of hundreds of patients treated with different agents), identify expression and epigenetic markers in tumors that predict response (by comparing expression and methylome arrays and kinase profiles in frozen tumor tissue from groups of patients who do (N=30) and do not (N=30) respond to different agents), to integrate these data from different platforms by means of bioinformatics and to conduct focused functional studies on the results in order to improve understanding of the critical molecular and resistance pathways involved. A large European consortium that has recruited and will recruit large numbers of patients ensures that the new markers identified in a first discovery phase can be tested in a subsequent replication phase. We have the ambition to define new validated risk stratification criteria to be used in personalized patient management. These criteria allow prediction of individual therapy response and resistance and will enable the monitoring of successful treatment outcome while reducing unnecessary drug use and expense.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-14-2015 | Award Amount: 7.97M | Year: 2016

Uveal melanoma (UM) is a rare intraocular tumour with an incidence of 5 cases per million individuals per year. Up to 50% of UM patients develop metastases, most often in the liver, and these are invariably fatal. Despite new discoveries in the genetic and molecular background of the primary tumour, little is known about the metastatic disease; furthermore, there is no therapy to either prevent or treat UM metastases. In UM Cure 2020, we aim to identify and validate at the preclinical level novel therapeutic approaches for the treatment of UM metastases. For this purpose, the consortium brings together the major experts of UM in both patient care and basic/translational/clinical research, as well as patient representatives. An ambitious multidisciplinary approach is proposed to move from patient tissue characterisation to preclinical evaluation of single or combinations of drugs. This approach includes the characterisation of the genetic landscape of metastatic UM and its microenvironment, proteomic studies to address signal pathway deregulation and establishment of novel relevant in vitro and in vivo UM models. We also aim to validate accurate surrogate endpoint biomarkers to evaluate therapies and detect metastases as early as possible. Underpinning this will be the UM Cure 2020 virtual biobank registry, linking existing biobanks into a harmonised network, which will prospectively collect primary and metastatic UM samples. Together, our approach will lead to the identification of new therapies, allowing the initiation of UM-dedicated clinical trials sponsored by academia or pharma. Dissemination of results will include the building of a patient network across the countries as part of the consortium as well as a dedicated UM patient and caregivers data portal as part of the UM Cure 2020 website, in order to increase patient information and disease awareness.

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