{"title":"Multiple myeloma: signaling pathways and targeted therapy.","authors":"Qizhong Lu, Donghui Yang, Hexian Li, Ting Niu, Aiping Tong","doi":"10.1186/s43556-024-00188-w","DOIUrl":null,"url":null,"abstract":"<p><p>Multiple myeloma (MM) is the second most common hematological malignancy of plasma cells, characterized by osteolytic bone lesions, anemia, hypercalcemia, renal failure, and the accumulation of malignant plasma cells. The pathogenesis of MM involves the interaction between MM cells and the bone marrow microenvironment through soluble cytokines and cell adhesion molecules, which activate various signaling pathways such as PI3K/AKT/mTOR, RAS/MAPK, JAK/STAT, Wnt/β-catenin, and NF-κB pathways. Aberrant activation of these pathways contributes to the proliferation, survival, migration, and drug resistance of myeloma cells, making them attractive targets for therapeutic intervention. Currently, approved drugs targeting these signaling pathways in MM are limited, with many inhibitors and inducers still in preclinical or clinical research stages. Therapeutic options for MM include non-targeted drugs like alkylating agents, corticosteroids, immunomodulatory drugs, proteasome inhibitors, and histone deacetylase inhibitors. Additionally, targeted drugs such as monoclonal antibodies, chimeric antigen receptor T cells, bispecific T-cell engagers, and bispecific antibodies are being used in MM treatment. Despite significant advancements in MM treatment, the disease remains incurable, emphasizing the need for the development of novel or combined targeted therapies based on emerging theoretical knowledge, technologies, and platforms. In this review, we highlight the key role of signaling pathways in the malignant progression and treatment of MM, exploring advances in targeted therapy and potential treatments to offer further insights for improving MM management and outcomes.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":null,"pages":null},"PeriodicalIF":6.3000,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11222366/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular biomedicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1186/s43556-024-00188-w","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Multiple myeloma (MM) is the second most common hematological malignancy of plasma cells, characterized by osteolytic bone lesions, anemia, hypercalcemia, renal failure, and the accumulation of malignant plasma cells. The pathogenesis of MM involves the interaction between MM cells and the bone marrow microenvironment through soluble cytokines and cell adhesion molecules, which activate various signaling pathways such as PI3K/AKT/mTOR, RAS/MAPK, JAK/STAT, Wnt/β-catenin, and NF-κB pathways. Aberrant activation of these pathways contributes to the proliferation, survival, migration, and drug resistance of myeloma cells, making them attractive targets for therapeutic intervention. Currently, approved drugs targeting these signaling pathways in MM are limited, with many inhibitors and inducers still in preclinical or clinical research stages. Therapeutic options for MM include non-targeted drugs like alkylating agents, corticosteroids, immunomodulatory drugs, proteasome inhibitors, and histone deacetylase inhibitors. Additionally, targeted drugs such as monoclonal antibodies, chimeric antigen receptor T cells, bispecific T-cell engagers, and bispecific antibodies are being used in MM treatment. Despite significant advancements in MM treatment, the disease remains incurable, emphasizing the need for the development of novel or combined targeted therapies based on emerging theoretical knowledge, technologies, and platforms. In this review, we highlight the key role of signaling pathways in the malignant progression and treatment of MM, exploring advances in targeted therapy and potential treatments to offer further insights for improving MM management and outcomes.
多发性骨髓瘤(MM)是浆细胞恶性肿瘤中第二常见的血液恶性肿瘤,以溶骨性骨病变、贫血、高钙血症、肾功能衰竭和恶性浆细胞聚集为特征。MM 的发病机制涉及 MM 细胞与骨髓微环境之间通过可溶性细胞因子和细胞粘附分子的相互作用,从而激活各种信号通路,如 PI3K/AKT/mTOR、RAS/MAPK、JAK/STAT、Wnt/β-catenin 和 NF-κB 通路。这些通路的异常激活导致骨髓瘤细胞的增殖、存活、迁移和耐药性,使它们成为有吸引力的治疗干预靶点。目前,针对 MM 这些信号通路的获批药物非常有限,许多抑制剂和诱导剂仍处于临床前或临床研究阶段。MM 的治疗选择包括非靶向药物,如烷化剂、皮质类固醇、免疫调节药物、蛋白酶体抑制剂和组蛋白去乙酰化酶抑制剂。此外,单克隆抗体、嵌合抗原受体T细胞、双特异性T细胞啮合剂和双特异性抗体等靶向药物也被用于MM的治疗。尽管 MM 的治疗取得了重大进展,但这种疾病仍然无法治愈,这就强调了基于新兴理论知识、技术和平台开发新型或联合靶向疗法的必要性。在这篇综述中,我们强调了信号通路在 MM 恶性进展和治疗中的关键作用,探讨了靶向治疗和潜在治疗的进展,为改善 MM 的管理和预后提供了进一步的见解。