Exportin-1 (XPO1) is a major transporter for hundreds of proteins. Selinexor is the first generation XPO1 inhibitor. At present, selinexor has gained more attention in the application of multiple myeloma (MM). Meanwhile, the latest clinical trials have confirmed that whether it is a single agent or combined with other chemotherapy regimens, selinexor can also achieve good therapeutic effects in patients with leukemia and lymphoma. This review summarizes the results of preclinical studies and clinical trials of selinexor in treatment of non-MM hematological malignancies, aiming to explore how to choose single agent or in combination with other regimens as induction chemotherapy.
UNASSIGNED: 塞利尼索在非多发性骨髓瘤血液肿瘤中的应用及研究进展.
UNASSIGNED: .核输出蛋白1（XPO1）是数百种蛋白质的主要转运蛋白。塞利尼索是第一代XPO1抑制剂，目前在多发性骨髓瘤的治疗中获得了较多的关注，同时最新临床试验也证实，无论是单药还是联合其他化疗方案，塞利尼索在白血病、淋巴瘤中同样能取得较好的治疗效果。本文总结了塞利尼索治疗非多发性骨髓瘤血液肿瘤的临床前研究和临床试验结果，旨在探讨未来如何选择塞利尼索单药或联合其他方案进行诱导化疗。.

OBJECTIVE: Selinexor is a novel XPO1 inhibitor which inhibits the export of tumor suppressor proteins and oncoprotein mRNAs, leading to cell-cycle arrest and apoptosis in cancer cells. While selinexor is currently FDA approved to treat multiple myeloma, compelling preclinical and early clinical studies reveal selinexor\'s efficacy in treating hematologic and non-hematologic malignancies, including sarcoma, gastric, bladder, prostate, breast, ovarian, skin, lung, and brain cancers. Current reviews of selinexor primarily highlight its use in hematologic malignancies; however, this review seeks to summarize the recent evidence of selinexor treatment in solid tumors.
METHODS: Pertinent literature searches in PubMed and the Karyopharm Therapeutics website for selinexor and non-hematologic malignancies preclinical and clinical trials.
RESULTS: This review provides evidence that selinexor is a promising agent used alone or in combination with other anticancer medications in non-hematologic malignancies.
CONCLUSIONS: Further clinical investigation of selinexor treatment for solid malignancies is warranted.

Cancer is the leading cause of death in economically developed countries and the second leading cause of death in developing countries. This global burden of cancer continues to increase largely because of the aging and growth of the world population. Although very much progress has been attained in the development of new therapies, there is a clear need of more efficient and selective antitumor drugs for the effective treatment of many types of cancer. Among the different strategies developed to create new antitumor drugs, pleiotropic non-genotoxic effectors have gained interest since this approach is less susceptible to known resistance mechanisms. The cell nucleus is the subcellular compartment where the genetic information and the transcription machinery reside and accordingly where numerous therapeutic agents efficiently work. Hence, nuclear-targeted drugs are expected to kill cancer cells more directly and efficiently. In this review, we discuss the potential of nuclear-targeted drugs as antineoplastic therapeutics and reason the benefits of the strategy to endow ribonucleases with cytotoxic properties based on its targeting into the nucleus.

Although tRNA was the first substrate whose export from the nuclei of eukaryotic cells had been shown to be carrier-mediated and active, it has only been in the last 2 years that the first mechanistic details of this nucleocytoplasmic transport pathway have begun to emerge. A member of the importin/karyopherin beta superfamily, Los1p in yeast and Xpo-t in vertebrates, has been shown to export tRNA in cooperation with the small GTPase Ran (Gsp1p) from the nucleus into the cytoplasm, where tRNA becomes available for translation. However, Los1p is not essential for viability in yeast cells, suggesting that alternative tRNA export pathways exist. Recent results show that aminoacylation and a translation factor are also required for efficient nuclear tRNA export. Thus, protein translation and nuclear export of tRNA appear to be coupled processes.