Targeting the early secretory pathway of multiple myeloma

Multiple myeloma (MM) is the second common hematologic malignancy and represents approximately 20% of deaths from blood cancers. Despite tremendous improvements in patient prognosis and treatment, the disease is still considered incurable in most cases. This situation is attributable mostly to the recurring nature of MM with reappearance of subclones resistant to previously used therapies. Therefore, identifying novel therapeutic strategies is crucial to increase progression-free and overall survival of MM patients. MM is characterized by the proliferation of abnormal bone marrow plasma cells and overproduction of immunoglobulins. These overproduced immunoglobulins need to leave the cell, and therefore MM cells are very good at secreting (releasing) proteins. Myeloma cells probably have the strongest secretory activity of any cell in the body. To cope with this challenge, myeloma cells have adapted their machinery that controls protein secretion. Therefore, myeloma cells can be described as addicted to secretion. The idea of this project is that myeloma cells can be killed by inhibiting secretion. To investigate this, I will first characterize which factors secrete immunoglobulins (also known as antibodies) and then examine whether the depletion of these factors can inhibit myeloma cell growth. All results obtained with immortalized culture cells will be confirmed using patient-derived cells. Through this project, I hope to identify a new therapeutic target for the treatment of multiple myeloma.