Abstract

Multiple Myeloma (MM) is an incurable disease with rapidly growing prevalence and poor prognosis. Consequently, it is the goal of the OPTATIO consortium to seek out novel strategies for the development of novel diagnostic and therapeutic options. The MM pathogenesis involves not only genetic changes within the tumour cells but also the emergence of supportive conditions by the bone marrow microenvironment (BMM). To target the essential components of this support system, it is the goal of the project to establish preclinical in vitro and in vivo models of MM that include functionally relevant elements of the BMM. The OPTATIO consortium will therefore analyse clinical data to correlate the presence of particular MM-BMM interactions with the pathogenesis of MM, with its intrinsic therapy resistance as well as with disease relapse due to the development of acquired drug resistance. These correlative data will be validated using autologous MM-BMM co-culture assays and reverse translated into in vitro screening and in vivo models, which will be subsequently used to develop lead compounds that target myeloma cells within their microenvironment. The clinical expertise of several oncological divisions, the research experience of academic laboratories and the pharmaceutical know-how of small and medium sized enterprises as well as biotech industry joined their efforts within the OPTATIO consortium to drive this important development and to ensure translation towards clinical trials. Expected impacts of the project include establishment of better diagnostics, new drug screening approaches for MM and novel personalised therapies based on individual ex vivo phenotyping leading to reduced patient mortality. Since envisaged drug screening methods are applicable to other areas of research and development, the project results will open new markets for industry partners in the fields of drug discovery and pharmaceutical development of products and services for personalized medicine.