Identification of epigenetic control mechanisms of Withaferin A dependent ferroptosis to overcome therapy resistance in multiple myeloma

Every year, over 22.000 people are diagnosed with multiple myeloma (MM). In this type of cancer, malignant plasma cells uncontrollably accumulate within the bone marrow causing devastating and often fatal symptoms. Although several therapies exist today that can improve quality of life and survival rate, the cancer cells frequently become resistant thus rendering the diseaseincurable. In this context, a new and promising anti-cancer drug class, known as epigenetic (modifying) drugs, is currently being investigated. In this novel treatment approach, the focus lies on restoring the distorted gene expression in the mutated plasma cells that is both responsible for the malignant character of the disease and increased therapy resistance. This project aims to resolve the mechanism of action of a novel class of epigenetic bioactive phytochemicals such as Withaferin A, which is able to overcome therapy resistance in MM. Of particular interest, recent studies in my lab (PPES) suggest that the therapeutic potential of Withaferin A lies in its ability to epigenetically alter gene expression and even induce cancer cell death via a novel alternative oxidative stress and iron-dependent form of cell death named "ferroptosis".Finally, by combining multiple innovative pharmacological (pharmacology on a chip), proteomic and epigenomic strategies, we aim to identify epigenetic control mechanisms of Withaferin A dependent ferroptosis to overcome therapy resistance in multiple myeloma.

Keywords:MYELOMA

Disciplines:Biochemistry and metabolism, Systems biology, Medical biochemistry and metabolism