Natural compounds and derivatives against multiple myeloma

Multiple myeloma is the second most common hematological malignancy with a median survival around 7 years. Standard treatments consist of autologous stem cell transplantation for eligible patients and combination therapies. Recent advances introduced immunotherapies such as monoclonal antibodies, immune checkpoint inhibitors and CAR T-cell products. Despite the expansion of novel pharmacological strategies, multiple myeloma patients still develop drug resistance and eventually relapse. As new treatment options against multiple myeloma are urgently needed, natural products can be investigated as a source of therapeutic agents with high chemical diversity and unique biological properties. One of our research lines focuses on natural products and their derivatives. Several models are used to evaluate the biological activity of these compounds, such as commercialized and primary multiple myeloma cells, as well as C. elegans. However, the surrounding cells in the bone marrow play a crucial role in supporting the survival, progression and chemoresistance of multiple myeloma cells. Therefore, cells from the tumor microenvironment are incorporated together with multiple myeloma cells into a 3D co-culture spheroid model to increase the predictive value of the biological evaluation. Compounds exhibiting selectivity towards multiple myeloma cells compared to healthy cells undergo mechanistic studies to explore potential novel targets in this malignancy. For the most promising compounds, pharmacokinetic followed by efficacy studies are performed in vivo. The goal of the present research topic is to bring new treatments to fight multiple myeloma.

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