Targeting inter-organelle communication to arrest multiple myeloma

Description

Multiple Myeloma (MM) is marked by the clonal expansion of abnormal plasma cells (PCs) in the bone marrow. It is the second most common hematologic malignancy, predominantly affecting the elderly, men, and Non-Hispanic Black individuals. While current treatments often induce remission, MM remains incurable, relapsing and causing chronic organ damage and high healthcare costs. Thus, new therapeutic targets are needed, especially for relapsed/refractory patients.
MM cells rely on inter-organelle communication to dispose of misfolded proteins and avoid lethal proteotoxic stress. Cancer can exploit this communication for growth and adaptation. Organelles communicate via vesicular carriers and direct contacts, ensuring protein progression, nutrient internalization, component recycling, and damage degradation. We hypothesize that some components of this system are essential for cell survival, while others are only needed under stress, such as in MM. We are evaluating whether targeting these dispensable components can effectively treat MM with limited toxicity.