Mechanisms and intervention strategies of microenvironment-mediated drug resistance in multiple myeloma

Multiple myeloma (MM) represents a common hematologic malignancy, and despite recent advancements in therapeutic strategies, drug resistance continues to adversely affect patient outcomes. Recent studies have underscored the critical role of the bone marrow microenvironment in the progression, drug resistance, and prognosis of MM. However, the mechanisms through which it facilitates drug resistance are still being extensively investigated. This article explores the MM microenvironment and the mechanisms underlying drug resistance, providing a detailed analysis of the composition, function, and principal mechanisms of microenvironment-mediated drug resistance in MM. These mechanisms encompass physical barriers and impediments to drug delivery, activation of intercellular signaling pathways, adhesion-mediated drug resistance, immunosuppressive microenvironments, metabolic reprogramming, epigenetic regulation, and clonal evolution. Furthermore, the article examines therapeutic strategies designed to target the microenvironment in order to overcome drug resistance. The objective is to provide a comprehensive overview of the current research status and emerging trends in this field, thereby serving as a reference for further in-depth research and the development of treatment strategies for MM.