Utilizing 3D Models to Unravel the Dynamics of Myeloma Plasma Cells' Escape from the Bone Marrow Microenvironment

Simple Summary New treatments have made a big difference in helping people with multiple myeloma (MM) live longer. In fact, survival rates have almost doubled compared with treatments before 2000, thanks to these new and effective medications. This means more people with MM are surviving for more than 10 years after being diagnosed. However, because people are living longer, some unusual situations are arising, like cancer coming back in places outside the bone marrow, such as organs, lymph nodes, and even the central nervous system. To better understand and treat these new challenges, scientists are using advanced 3D models, especially looking at the bone marrow and other places where cancer may show up. This review identifies the best ways to use these 3D models, discusses the difficulties in recreating the complexity of the disease, and emphasizes how these advanced models can help fight MM.Abstract Recent therapeutic advancements have markedly increased the survival rates of individuals with multiple myeloma (MM), doubling survival compared to pre-2000 estimates. This progress, driven by highly effective novel agents, suggests a growing population of MM survivors exceeding the 10-year mark post-diagnosis. However, contemporary clinical observations indicate potential trends toward more aggressive relapse phenotypes, characterized by extramedullary disease and dominant proliferative clones, despite these highly effective treatments. To build upon these advances, it is crucial to develop models of MM evolution, particularly focusing on understanding the biological mechanisms behind its development outside the bone marrow. This comprehensive understanding is essential to devising innovative treatment strategies. This review emphasizes the role of 3D models, specifically addressing the bone marrow microenvironment and development of extramedullary sites. It explores the current state-of-the-art in MM modelling, highlighting challenges in replicating the disease's complexity. Recognizing the unique demand for accurate models, the discussion underscores the potential impact of these advanced 3D models on understanding and combating this heterogeneous and still incurable disease.