Tasbihi Kereshmeh, Bruns Heiko
Department of Medicine 5-Hematology and Oncology, University Hospital Erlangen, 91054 Erlangen, Germany.
Cells. 2025 Mar 13;14(6):430. doi: 10.3390/cells14060430.
Despite the major advancements in the repertoire for multiple myeloma (MM) treatment, this disease remains a chronically progressive plasma cell malignancy. Drug resistance and high relapse rates complicate the extended treatment strategies. However, the tumor microenvironment (TME) in MM is decisive for the success of a therapy or relapse. Aiming to improve the outcome of relapsed and refractory MM patients, Selinexor has entered the drug arsenal of myeloma therapy through the implementation of a novel therapeutic approach by selectively inhibiting the nuclear export receptor Exportin-1 (XPO1). Selinexor leads to the inactivation of cancer-related proteins and induces apoptosis by disrupting the nucleocytoplasmic flow in myeloma cells. While this drug is selectively cytotoxic to neoplastic cells, Selinexor's immunomodulatory impact on the TME is currently being investigated. The aim of this review was to elucidate Selinexor's capacity to influence the cell interaction network of the TME from an immunological perspective. Deciphering the complex interplay of highly plastic immune cells provides a contribution to the molecular-biological exploration of disease initiation and progression in MM. Unraveling the novel therapeutic targets of the immunological TME and evaluating the advanced immunotherapeutic regimens implementing Selinexor will shape the future directions of immune-oncotherapy in MM.
尽管多发性骨髓瘤（MM）治疗方法取得了重大进展，但这种疾病仍然是一种慢性进展性浆细胞恶性肿瘤。耐药性和高复发率使延长治疗策略变得复杂。然而，MM中的肿瘤微环境（TME）对治疗成功或复发起着决定性作用。为了改善复发和难治性MM患者的治疗效果，塞利尼索通过选择性抑制核输出受体Exportin-1（XPO1）实施了一种新的治疗方法，从而进入了骨髓瘤治疗的药物库。塞利尼索导致癌症相关蛋白失活，并通过破坏骨髓瘤细胞中的核质流动诱导细胞凋亡。虽然这种药物对肿瘤细胞具有选择性细胞毒性，但目前正在研究塞利尼索对TME的免疫调节作用。本综述的目的是从免疫学角度阐明塞利尼索影响TME细胞相互作用网络的能力。解读高度可塑性免疫细胞的复杂相互作用有助于对MM疾病发生和进展进行分子生物学探索。揭示免疫TME的新治疗靶点并评估实施塞利尼索的先进免疫治疗方案将塑造MM免疫肿瘤治疗的未来方向。
