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PROTEOMIC IDENTIFICATION OF BIOMARKERS IN BIOFLUIDS AND IN PRECLINICAL MODELS FOR THE EARLY DIAGNOSIS AND PROGNOSIS OF CANCER (PROT*BIO*FLUID)

Final Report Summary - PROTBIOFLUID (PROTEOMIC IDENTIFICATION OF BIOMARKERS IN BIOFLUIDS AND IN PRECLINICAL MODELS FOR THE EARLY DIAGNOSIS AND PROGNOSIS OF CANCER (PROT*BIO*FLUID))

PROTBIOFLUID is a network for developing innovative early diagnostic techniques and forspreading this knowledge through the medical community by a systematic exchange of staff to create high impact benefits to patients and transform the way endometrial, ovarian, prostate and bladder cancers are managed. The necessity of this project comes from the observation that 1.6 million people are killed worldwide each year due to ovarian, endometrial, bladder and prostate cancers. We believe that the key to making treatment breakthrough is early diagnosis.
Our overall science objective is to study biofluids in cancer patients in order to determine specific proteomic profiles to lay the foundation for the development of a simple to use diagnostic tool that will become ubiquitous in the medium-to-long-term.
Our objectives to create this impact are:
1- Establish new methods for proteomic identification of biomarkers in biofluids for the early diagnosis and prognosis of cancer
2- Evaluate molecular markers and therapeutic targets of metastasis through the use of preclinical animal models
Currently the know-how to reach these objectives exists but the field is highly fragmented. IRSES project has been useful so far as a catalyst for a focused network to create the critical mass to solve very pressing treatment problems. This network is mainly composed by leading research partners with established relations of trust and reciprocity and who bring the correct combinations of complementary expertise. Since the beginning of the project, mostly researcher at earlier phases of their career have performed exchanges to effect the interlinking of research lines to finally achieve both high level knowledge exchanges as well as knowledge transfer through teaching and ‘hands on’ experience of best practice. As a result of these exchanges, the project itself has grown in dimension as new approaches have been delineated for each objective. The main results obtained since the beginning of the project in relation to improve diagnosis in these cancers include the definition of three strategies for the identification of diagnostic markers in endometrial and prostate cancers, as well as the identification of prognostic markers in ovarian cancer. We have finalized the identification of markers which could be used in diagnosis and prognosis markers by means of proteomics, and we have optimized the methods needed to pursue other mass spectrometry approaches, i.e. metabolomics. In terms of treatment, we have successfully characterized molecular events associated to myometrial infiltration in vitro and in vivo associated to ETV5 transcription factor, as this gene is upregulated in invasive ECs. Special attention has been paid to E-Cadherin in all tumours, as this tumour suppressor is a key molecule in Epithelial to Mesenchymal Transition (EMT), a process that triggers tumour invasion in many types of cancer. Some preliminary have observed that the relation between E-cadherin transcripts and other EMT markers contributes to the tumour diagnosis and prognosis. In order to evaluate future therapies, we have developed prostate and endometrial animal models that can be followed-up in vivo to study the progression of the tumour. This tool will permit in vivo monitoring of drug efficiency as well as characterize the role of specific targets.
At the end of the PROTBIOFLUID we have agreed a framework for joint programming between partner institutions. The nucleus of this consortium has been capable to identify biomarkers and molecular pathways, as well as develop relevant preclinical models, that will be the basis to develop diagnostic tools and treatment options for these deadly cancers.