Dadzie Terry G, Green Alanna C
Weston Park Cancer Centre and Mellanby Centre for Musculoskeletal Research, Department of Oncology and Metabolism, The Medical School, University of Sheffield, Sheffield, United Kingdom.
Front Oncol. 2022 Aug 22;12:999939. doi: 10.3389/fonc.2022.999939. eCollection 2022.
Multiple myeloma is an incurable haematological cancer. The increase in targeted therapies has improved the number of myeloma patients achieving a complete response and improved progression-free survival following therapy. However, a low level of disease or minimal residual disease (MRD) still persists which contributes to the inevitable relapse in myeloma patients. MRD has been attributed to the presence of dormant myeloma cells and their subsequent reactivation, which is controlled by the microenvironment and specialised niches within the bone marrow. This contributes to the evasion of the immune system and chemotherapy, eventually leading to relapse. The growth of myeloma tumours are heavily dependent on environmental stimuli from the bone marrow microenvironment, and this plays a key role in myeloma progression. The bone microenvironment also plays a critical role in myeloma bone disease and the development of skeletal-related events. This review focuses on the bone marrow microenvironment in relation to myeloma pathogenesis and cancer dormancy. Moreover, it reviews the current therapies targeting the bone microenvironment to treat myeloma and myeloma bone disease. Lastly, it identifies novel therapeutic targets for myeloma treatment and the associated bone disease.
多发性骨髓瘤是一种无法治愈的血液系统癌症。靶向治疗的增加提高了实现完全缓解的骨髓瘤患者数量，并改善了治疗后的无进展生存期。然而，疾病的低水平或微小残留病（MRD）仍然存在，这导致骨髓瘤患者不可避免地复发。MRD归因于休眠骨髓瘤细胞的存在及其随后的重新激活，这由骨髓内的微环境和特殊龛所控制。这有助于逃避免疫系统和化疗，最终导致复发。骨髓瘤肿瘤的生长严重依赖于骨髓微环境的环境刺激，这在骨髓瘤进展中起关键作用。骨微环境在骨髓瘤骨病和骨相关事件的发展中也起关键作用。本综述重点关注与骨髓瘤发病机制和癌症休眠相关的骨髓微环境。此外，它回顾了目前针对骨微环境治疗骨髓瘤和骨髓瘤骨病的疗法。最后，它确定了骨髓瘤治疗及相关骨病的新治疗靶点。
