PMID- 37126200 OWN - NLM STAT- MEDLINE DCOM- 20230831 LR - 20230902 IS - 1559-0283 (Electronic) IS - 1085-9195 (Linking) VI - 81 IP - 3 DP - 2023 Sep TI - Nuclear Export Inhibitors Selinexor (KPT-330) and Eltanexor (KPT-8602) Provide a Novel Therapy to Reduce Tumor Growth by Induction of PANoptosis. PG - 421-426 LID - 10.1007/s12013-023-01135-2 [doi] AB - Programmed cell death (PCD) is a process that occurs naturally in cells in response to different endogenous or exogenous factors and facilitated by specific proteins. The three common pathways are pyroptosis, necroptosis, and apoptosis. Each pathway has its own unique proteins, mechanisms, and byproducts. Dysregulated PCD can lead to abnormal growth of cells causing tumor growth, a hallmark feature of many cancer pathologies. Recently, the PCD pathways have been considered to be activated simultaneously in a combined nature defined as PANoptosis (pyroptosis, apoptosis, and necroptosis). An integral protein, Z-DNA binding protein 1 (ZBP1) aids in the initiation of the NOD-like receptor protein 3 (NLRP3) inflammasome, a known facilitator of pyroptosis. It also is known to bind to a regulator of necroptosis, receptor-interacting protein kinase 3 (RIPK3). A unique binding partner to ZBP1, adenosine deaminase acting on RNA 1 (ADAR1), is involved in RNA editing, stress mechanisms, and disease. In murine bone marrow-derived macrophages (BMDMs) treatment with nuclear export inhibitors (NEIs) has allowed for sequestering of ADAR1 to the nucleus, and increased incidence of cell death. Additionally, the use of interferons (IFNs) to induce ZBP1 has increased the incidence of cell death. Emerging therapies are looking at the efficacy of using a combination of NEI and IFN treatment to rapidly reduce tumor size and growth by inducing PANoptosis. KPT-330 and KPT-8602 are two different NEIs, both of which have shown efficacy in the reduction of tumor size and inhibition of Exportin 1 (XPO1), a transport protein. However, this article posits KPT-8602 as the better of the two. KPT-8602 is more tolerable for the patient and should be pushed to human trials. CI - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Camilli, Samuel AU - Camilli S AD - Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA. FAU - Lockey, Richard AU - Lockey R AD - Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA. FAU - Kolliputi, Narasaiah AU - Kolliputi N AD - Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA. nkollipu@usf.edu. LA - eng PT - Journal Article PT - Review DEP - 20230501 PL - United States TA - Cell Biochem Biophys JT - Cell biochemistry and biophysics JID - 9701934 RN - 31TZ62FO8F (selinexor) RN - 0 (Eltanexor) RN - 0 (Antineoplastic Agents) RN - EC 3.5.4.4 (ADAR1 protein, mouse) RN - EC 3.5.4.4 (Adenosine Deaminase) SB - IM MH - Humans MH - Animals MH - Mice MH - Active Transport, Cell Nucleus MH - *Antineoplastic Agents/pharmacology/therapeutic use MH - Cell Line, Tumor MH - Apoptosis MH - Adenosine Deaminase OTO - NOTNLM OT - Cell death OT - Tumor EDAT- 2023/05/01 12:43 MHDA- 2023/08/31 06:42 CRDT- 2023/05/01 11:08 PHST- 2022/06/13 00:00 [received] PHST- 2023/04/12 00:00 [accepted] PHST- 2023/08/31 06:42 [medline] PHST- 2023/05/01 12:43 [pubmed] PHST- 2023/05/01 11:08 [entrez] AID - 10.1007/s12013-023-01135-2 [pii] AID - 10.1007/s12013-023-01135-2 [doi] PST - ppublish SO - Cell Biochem Biophys. 2023 Sep;81(3):421-426. doi: 10.1007/s12013-023-01135-2. Epub 2023 May 1.