Developing novel ferroptosis chemosensitization strategies and phospho-catalytic kinome diagnostic tools for improved therapeutic outcome in multiple myeloma.

Multiple myeloma (MM) is a B-cell malignancy characterized by the accumulation of a clone of malignant plasma cells in the bone marrow. Despite the progress in therapy, MM remains largely incurable. Conventional therapies with proteasome inhibitors (bortezomib), immunomodulatory drugs (thalidomide, lenalidomide), epigenetic drugs (Velcade), corticosteroids, and alkylating agents (melphalan) are associated with low remission rates, limited survival times (approx. 5 years) and the development of drug resistance. In the current project, pharmacological and biophysical (plasma) ferroptosis strategies will be optimized for MM chemosensitisation and/or immunogenic therapeutic approaches in MM cell lines (in vitro), MM patient samples (ex vivo) and preclinical MM mouse models (in vivo). In addition, a novel phospho-catalytic kinome activity mapping approach will be developed using biological peptide targets as phospho-sensors which allow kinome level quantification of redox specific changes in tyrosine kinase activities following ferroptosis chemosensitisation and/or immunisation in the different experimental therapeutic setups. Moreover, this phosphopeptide fingerprint can be applied as a diagnostic and/or predictive biomarker for personalized medicine applications for improved therapeutic outcome in MM patients

Keywords:TUMOR VACCINE, THERAPY RESISTANCE, TUMOR MARKER, ANTI TUMOR DRUGS

Disciplines:Cell death, Cell signalling