Speaker
Description
Multiple myeloma is a hematological malignancy that primarily impacts older individuals. Despite this, preclinical models often use younger animals that do not accurately represent the aged bone microenvironment in which the disease flourishes. Aging in the bone microenvironment is characterized by changes in bone structure, altered remodeling mechanisms, and increased cellular senescence. This work uses a hybrid agent-based model to capture these age-induced transformations in the bone microenvironment and assess their impact on multiple myeloma progression. Cell types involved in bone remodeling, such as osteoblasts, osteoclasts, and mesenchymal stem cells, are modeled alongside signaling of RANKL and bone-derived factors. The model is parameterized with data from aged tumor-naive and 5TGM1-inoculated C57BL/KaLwRij mice representative of the average age of a myeloma patient. We first modify the simulated bone microenvironment to reflect homeostatic bone remodeling and trabecular bone architecture in an aged disease-free patient. Next, we introduce multiple myeloma cells to assess disease progression in the aged simulated microenvironment. We model the impact of zoledronate, a bisphosphonate used in the standard of care regimen for multiple myeloma, on aged bone remodeling, tumor burden, and the development of environment-mediated drug resistance. This work emphasizes the importance of accounting for age-dependent changes in parameters in computational models.
