Targeting bone marrow adipose tissue and the FABP family increases efficacy of dexamethasone in MM
Maine Medical Center, Medical Education, Maine Medical Center Research Institute
Bone Marrow, Dexamethasone, Adipose Tissue, Bone Marrow Cells
• Multiple myeloma (MM) is an incurable cancer of plasma cells. Myeloma cells grow primarily in the bone marrow (BM) and home throughout the body to extramedullary locations. MM causes aberrant IgG production, renal failure, hypercalcemia, anemia, and bone destruction. MM patients almost always relapse with the disease; finding new ways to target drug resistant MM clones is a major clinical need.
• Bone Marrow Adipocytes (BMAs) have been shown to be supportive of MM cells and are associated with the transitions of both MGUS to MM and remission to relapse, with a strong correlation between high BMI and poor treatment response (Liu et al, Sci. Transl. Med, 2019).
• As BMAs have been shown to be supportive in other cancers, such as AML and prostate cancer, therapeutically targeting the BM adipocyte may prove to be revolutionary in the clinic for treating MM.
• Fatty Acid Binding Protein (FABP) family members have been linked to increased fatty acid trafficking and act as signaling molecules in many different malignant cells (Furuhashi, Nature, 2007).
• Objective: Determine the role of BMAs in MM disease progression and discover novel targets to overcome drug resistance and relapse in MM.
• Hypotheses: 1) BMAs secrete soluble factors that alter normal MM signaling to induce proliferation and/or dexamethasone resistance; 2) fatty acid binding protein family signaling is involved in the response of MM cells to BMAs and may be a novel therapeutic avenue in MM.
Farrell, Mariah; Fairfield, Heather; Falank, Carolyne; Costa, Samantha; D’Amico, Anastasia; Bowers, Dominic; and Reagan, Michaela R., "Targeting bone marrow adipose tissue and the FABP family increases efficacy of dexamethasone in MM" (2020). Costas T. Lambrew Research Retreat 2020. 38.
2020 Costas T. Lambrew Research Retreat