Our recent studies have identified specific bacteria that can potentially promote the growth of human myeloma tumor cells. We are now testing if eradicating these bacteria in MGUS patients will be effective for prevention of myeloma.
In the past decade, there have been major improvements in outcomes for myeloma patients. However the underlying cause of myeloma remains unknown. All cases of myeloma originate from a precursor stage called monoclonal gammopathy of undetermined significance (MGUS). This application builds on our prior studies showing that aberrant activation of the immune system sets the stage for development of initially the precursor stage and then eventual development of myeloma. One possibility is that bacteria in the stool provide triggers that can drive growth of tumor cells. The stool typically consists of billions of bacteria, and these include both good bugs and bad bugs. In recent preliminary studies, we have identified some candidate bad bugs that may contribute to tumor growth. This led us to initiate a clinical trial targeting bacteria in patients with MGUS. This application seeks support for an academic clinical trial wherein we will test whether a short course of antibiotics can reduce bad bugs and change the trajectory of MGUS. If successful, these studies will provide the basis for future lifestyle based interventions to prevent myeloma. These studies may also have implications for pathogenesis and prevention of other blood cancers such as "B cell lymphomas" in humans.