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Third-party-funded project

Title:
Functional characterisation of oncogenic signalling pathways in primary myeloma cells: identification of biomarkers and therapeutically relevant targets

Project management at the University of Würzburg:

Participating scientists:

Abstract:
The aim of this study is a systematic analysis in primary human myeloma cells of the IL‑6R/STAT3‑, the Ras/MAPK- and the PI3K/Akt-signalling pathways, which in cell line models have all been implicated in the pathophysiology of multiple myeloma. We plan to investigate whether the bone marrow microenvironment actually activates these pathways in primary tumour cells and if their selective pharmacological blockade is sufficient under these conditions to promote apoptotic death of the myeloma cells. Furthermore, we wish to analyse if HSP90 blockade is an appropriate means to impair maintenance of the oncogenic signalling network in primary myeloma cells and if this, too, causes apoptosis even in the context of the bone marrow microenvironment. Finally, we wish to examine the role(s) of the different Akt isoforms (Akt1, 2 and 3), whose specific contributions to the pathophysiology of myeloma are entirely unclear. This work should help to identify and characterise potentially useful targets for therapeutic intervention. It should also provide a framework for the assessment of biomarkers and for pharmacodynamics analyses, which will be conducted in future Phase-I studies with pharmacologic inhibitors of the above-mentioned pathways

Key words:
    Multiple Myeloma

Projekt period: from 05.2007 to 05.2009

Funding institution:
Sonstige Stiftung ( Novartis ) ,Granting date: 24.01.2007