This proposal brings together the translational medicine expertise of Dana-Farber Cancer Institute (DFCI) with the clinical research strength of Intergroupe Francophone du Myeloma (IFM) in France and the genomics expertise of the Sanger Institute in the UK to develop a curative strategy for MM. In the proposed international collaborative project, we will initiate the most important clinical trial in MM to date, integrating bortezomib, lenalidomide and dexamethasone with high dose therapy in an effort to pursue cure in MM (Project 1). This trial will provide 1000 MM and normal cell samples from newly diagnosed and uniformly treated patients to comprehensively characterize the MM genome and to define molecular events driving development and progression of MM (Project 2);to identity novel therapeutic targets and agents (Project 3) and biomarkers (Projects 1,2,4);as well as to define the mechanism and clinical implications of genomic instability in MM (Project 4). The ultimate goal of the research projects in this program is to identify oncogenomic changes and their relationship with clinical outcome;and to identify and develop innovative therapies targeting molecular abnormalities in MM. This unique collaborative effort requires significant coordination of effort, integration of strategies, monitoring and oversight of various functions, and communication between investigators at various dispersed sites. The key function of Core A is integration of the research efforts and communication between investigators. Scientific and administrative integration is essential to assure successful interaction between the four Projects, as well as between the laboratory and clinical components within and between projects in this multinational multi-institutional program. Therefore, this central core will provide the link between various projects and successfully co-ordinate the clinical study and the proposed correlative science. To aid in achieving these goals. Core A will: monitor the timely conduct of the clinical study and assure progress in tissue collection, processing and usage to co-ordinate interaction between the clinical and correlative science studies (Specific Aim 1);provide necessary resources, fiscal oversight and administrative support for projects and cores (Specific Aim 2);co-ordinate communication, and exchange of data between investigators at various international sites (Specific Aim 3);facilitate intra-programatic interactions, meetings, travel and Internal and External Advisory Committees (Specific Aim 4).
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