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• W4210660520 endingPage "612" @default.
• W4210660520 startingPage "601" @default.
• W4210660520 abstract "Novel targeted therapeutics alone or in rational combinations are likely to dominate the future management of various hematological neoplasms. However, the challenges currently faced are the molecular heterogeneity in driver lesions and genetic plasticity leading to multiple resistance pathways. Thus, progress has overall been gradual. For example, despite the advent of targeted agents against actionable drivers like FLT3 in acute myeloid leukemia (AML), the prognosis remains suboptimal in newly diagnosed and dismal in the relapsed/refractory (R/R) setting, due to other molecular abnormalities contributing to inherent and acquired treatment resistance. Nuclear export inhibitors are of keen interest because they can inhibit several active tumorigenic processes simultaneously and also synergize with other targeted drugs and chemotherapy. XPO1 (or CRM1, chromosome maintenance region 1) is one of the most studied exportins involved in transporting critical cargoes, including tumor suppressor proteins like p27, p53, and RB1. Apart from the TSP cargo transport and its role in drug resistance, XPO1 inhibition results in retention of master transcription factors essential for cell differentiation, cell survival, and autophagy, rendering cells more susceptible to the effects of other antineoplastic agents, including targeted therapies. This review will dissect the role of XPO1 inhibition in hematological neoplasms, focusing on mechanistic insights gleaned mainly from work with SINE compounds. Future potential combinatorial strategies will be discussed." @default.
• W4210660520 created "2022-02-08" @default.
• W4210660520 creator A5026049304 @default.
• W4210660520 creator A5083571797 @default.
• W4210660520 creator A5085974329 @default.
• W4210660520 date "2022-01-29" @default.
• W4210660520 modified "2023-10-14" @default.
• W4210660520 title "Selective inhibition of nuclear export: a promising approach in the shifting treatment paradigms for hematological neoplasms" @default.
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