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Selinexor in acute myeloid leukemia: therapeutic applications and current challenges.

This article aims to review the current application status and research advancements of selinexor in the treatment of acute myeloid leukemia (AML). Selinexor, as the first oral selective inhibitor of nuclear export protein Exportin-1 (XPO1), inhibits the abnormal nuclear export of tumor suppressor proteins by blocking XPO1, thereby restoring their activity and exerting antitumor effects. Clinical studies have shown that selinexor monotherapy or combination therapy has demonstrated good anti-leukemia effects in AML, especially in patients with relapsed/refractory AML. In addition, the combinati

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… Realgar-indigo naturalis formula for the treatment of patients with relapsed and arsenic trioxide-resistant acute promyelocytic leukemia: a case series. J. Integr. …

Fate of hematopoietic stem cells determined by Notch1 signaling (Review).

Regulation of the fate of hematopoietic stem cells (HSCs), including silencing, self-renewal or differentiation into blood line cells, is crucial to maintain the homeostasis of the human blood system and prevent leukemia. Notch1, a key receptor in the Notch signaling pathway, plays an important regulatory role in these properties of HSCs, particularly in the maintenance of the stemness of HSCs. In recent decades, the ubiquitination modification of Notch1 has been gradually revealed, and also demonstrated to affect the proliferation and differentiation of HSCs. Therefore, a detailed elucidation

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… Arsenic trioxide inhibits Hedgehog, Notch and stem cell properties in glioblastoma neurospheres. Acta Neuropathologica Communications. 2014;2(31) doi: 10.1186/2051-5960-2-31. 140. Liu H, Zhu L, Liu YH. …

Chimeric Antigen Receptor T-cell Therapy in Hematologic Malignancies and Patient-reported Outcomes: A Scoping Review.

The inclusion of patient-reported outcome (PRO) measures in chimeric antigen receptor (CAR) T-cell therapy research is critical for understanding the impact of this novel approach from a unique patient standpoint. We performed a scoping review to map the available literature on the use of PRO measures in CAR T-cell therapy studies of patients with hematologic malignancies published between January 2015 and July 2022. Fourteen studies were identified, of which 7 (50%) were investigational early-phase trials, 6 (42.9%) were observational studies, and 1 (7.1%) was a pilot study. The EQ-5D and the

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… Randomized phase III trial of retinoic acid and arsenic trioxide versus retinoic acid and chemotherapy in patients with acute promyelocytic leukemia: health-related quality-of-life outcomes. J Clin Oncol. 2014;32:3406–3412. 65. Kantarjian HM, Su Y, Jabbour EJ, et al. …

Non-Hematologic Toxicity of Bortezomib in Multiple Myeloma: The Neuromuscular and Cardiovascular Adverse Effects.

The overall approach to the treatment of multiple myeloma (MM) has undergone several changes during the past decade. and proteasome inhibitors (PIs) including bortezomib, carfilzomib, and ixazomib have considerably improved the outcomes in affected patients. The first-in-class selective PI bortezomib has been initially approved for the refractory forms of the disease but has now become, in combination with other drugs, the backbone of the frontline therapy for newly diagnosed MM patients, as well as in the maintenance therapy and relapsed/refractory setting. Despite being among the most widely

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… A Phase I/II Study of Arsenic Trioxide/Bortezomib/Ascorbic Acid Combination Therapy for the Treatment of Relapsed or Refractory Multiple Myeloma Clin. Cancer Res. 2007 13 1762 1768 10.1158/1078-0432.CCR-06-1812 17363530 125. Takamatsu H. Yamashita T. Kotani T. Sawazaki A. Okumura H. Nakao S. …

HDAC3: A Multifaceted Modulator in Immunotherapy Sensitization.

Histone deacetylase 3 (HDAC3) has emerged as a critical epigenetic regulator in tumor progression and immune modulation, positioning it as a promising target for enhancing cancer immunotherapy. This work comprehensively explores HDAC3's multifaceted roles, focusing on its regulation of key immune-modulatory pathways such as cGAS-STING, ferroptosis, and the Nrf2/HO-1 axis. These pathways are central to tumor immune evasion, antigen presentation, and immune cell activation. Additionally, the distinct effects of HDAC3 on various immune cell types-including its role in enhancing T cell activation,

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… Arsenic trioxide augments immunogenic cell death and induces cGAS-STING-IFN pathway activation in hepatocellular carcinoma Cell Death Dis. 2024 15 300 10.1038/s41419-024-06685-8 38684648 PMC11058202 83. Jiang M. Chen P. Wang L. Li W. Chen B. Liu Y. Wang H. Zhao S. Ye L. …

Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.

Nuclear receptors (NRs) are a large family of ligand-dependent transcription factors that regulate the expression of a wide range of target genes in response to endogenous and exogenous ligands, including steroid hormones, thyroid hormone, vitamin D, retinoic acid, fatty acids, and oxidative steroids. Upon ligand binding, nuclear receptors form dimer complexes with transcriptional cofactors, which interact with specific DNA sequences in the promoter or enhancer regions of target genes to modulate gene expression. This process plays a crucial role in many physiological processes such as reprodu

From Lab to Clinic: Success Stories of Repurposed Drugs in Treating Major Diseases.

Drug repurposing, the process of identifying new therapeutic uses for existing drugs, has emerged as a cost-effective and time-saving alternative to traditional drug development. This strategy leverages the known pharmacological and safety profiles of approved or investigational drugs to accelerate their clinical application for other diseases. In recent years, repurposed drugs have played a crucial role in addressing treatment gaps in complex and multifactorial diseases such as cancer, neurodegenerative disorders and infectious diseases. This review highlights prominent examples where repurpo

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… Studies have identified potential candidates like carvedilol, andrographolide, 2‐methoxyestradiol, etanercept, polaprezinc and arsenic trioxide [ 33 ]. In the context of COVID‐19, there has been an exploration of DRP strategies aimed at identifying broad‐spectrum antivirals. …

Prevalence, Attributes, and Risk Factors of QT-Interval-Prolonging Drugs and Potential Drug-Drug Interactions in Cancer Patients: A Prospective Study in a Tertiary Care Hospital.

Introduction Cancer chemotherapy regimens include multiple classes of adjuvant drugs as supportive therapy. Because of the concurrent intake of other drugs (like antiemetics, antidepressants, analgesics, and antimicrobials), there is a heightened risk for possible QT interval prolongation. There is a dearth of evidence in the literature regarding the usage of QT-prolonging anticancer drugs and associated risk factors that have the propensity to prolong QT interval. The purpose was to explore the extent of the use of QT-interval-prolonging drugs and potential QT-prolonging drug-drug interaction

Взгляды заинтересованных сторон Соединенного Королевства на суррогатные концы рака и потенциальные возможности Соединенного Королевства в области реальных мировых данных для подтверждения их использования в процессе принятия решений.

Продолжительность общего выживаемости пациентов с раком увеличилась благодаря более раннему обнаружению и совершенствованию лечения. Однако эти улучшения породили трудности с оценкой воздействия новых методов лечения, особенно тех, которые используются на раннем этапе лечения. Поскольку общее выживание остается предпочтительным для большинства лиц, принимающих решения, для внедрения в практику клинической практики терапевтических инноваций может потребоваться много времени. Кроме того, трудно экстраполировать полученные результаты на разнородные группы населения и решить проблемы пациентов, же

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… Prospective minimal residual disease monitoring to predict relapse of acute promyelocytic leukemia and to direct pre-emptive arsenic trioxide therapy. J Clin Oncol . 2009;27(22):3650–3658. doi: 10.1200/JCO.2008.20.1533 79. Smith G, Apperley J, Milojkovic D, et al. …

Targeted Drug Delivery and Theranostic Strategies in Malignant Lymphomas.

Malignant lymphomas represent the most common type of hematologic malignancies. The first clinically approved TDD modalities in lymphoma patients were anti-CD20 radioimmunoconjugates (RIT) 131I-tositumomab and 90Y-ibritumomab-tiuxetan. The later clinical success of the first approved antibody-drug conjugate (ADC) for the treatment of lymphomas, anti-CD30 brentuximab vedotin, paved the path for the preclinical development and clinical testing of several other ADCs, including polatuzumab vedotin and loncastuximab tesirine. Other modalities of TDD are based on new formulations of "old" cytostatic

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… GO is currently being evaluated in numerous clinical trials in combination with chemotherapy or targeted agents for patients with newly diagnosed and treatment-refractory AML, including CPX-351 ( NCT03904251 ), venetoclax ( NCT04070768 ), arsenic trioxide plus all trans-retinoic acid ( NCT01409161 ), …

Dual Roles of NIX/BNIP3L in Tumors: Friend or Foe.

Cancer is one of the leading causes of disease-related death worldwide, and targeting key regulatory genes to induce programmed cell death in tumor cells has emerged as a crucial therapeutic strategy, following surgery, radiotherapy, and chemotherapy. As a mitochondrial outer membrane protein, NIX/BNIP3L can both mediate apoptosis to inhibit tumor cell growth and promote tumor cell survival by clearing intracellular reactive oxygen species (ROS) through mitophagy. Therefore, we summarize a brief overview of the structure and function of NIX/BNIP3L, as well as the mechanisms of NIX/BNIP3L gener

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… Arsenic trioxide induces autophagic cell death in malignant glioma cells by upregulation of mitochondrial cell death protein BNIP3. Oncogene. 2004;24:980–991. doi: 10.1038/sj.onc.1208095. 56. Han B., Zheng R., Zeng H., Wang S., Sun K., Chen R., Li L., Wei W., He J. …

Recent Perspectives on Cardiovascular Toxicity Associated with Colorectal Cancer Drug Therapy.

Cardiotoxicity is a well-known adverse effect of cancer-related therapy that has a significant influence on patient outcomes and quality of life. The use of antineoplastic drugs to treat colorectal cancers (CRCs) is associated with a number of undesirable side effects including cardiac complications. For both sexes, CRC ranks second and accounts for four out of every ten cancer deaths. According to the reports, almost 39% of patients with colorectal cancer who underwent first-line chemotherapy suffered cardiovascular impairment. Although 5-fluorouracil is still the backbone of chemotherapy reg

Aminoquinolines as Translational Models for Drug Repurposing: Anticancer Adjuvant Properties and Toxicokinetic-Related Features.

The indiscriminate consumption of antimalarials against coronavirus disease-2019 emphasizes the longstanding clinical weapons of medicines. In this work, we conducted a review on the antitumor mechanisms of aminoquinolines, focusing on the responses and differences of tumor histological tissues and toxicity related to pharmacokinetics. This well-defined analysis shows similar mechanistic forms triggered by aminoquinolines in different histological tumor tissues and under coexposure conditions, although different pharmacological potencies also occur. These molecules are lysosomotropic amines th

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… Arsenic trioxide and thalidomide combination induce autophagy along with apoptosis in acute myeloid cell lines. Cell Journal. 2020;22:193–202. doi: 10.22074/cellj.2020.6469. 18. Jiang F., Xing H. S., Chen W. Y., et al. …

Zebrafish Avatars towards Personalized Medicine-A Comparative Review between Avatar Models.

Cancer frequency and prevalence have been increasing in the past decades, with devastating impacts on patients and their families. Despite the great advances in targeted approaches, there is still a lack of methods to predict individual patient responses, and therefore treatments are tailored according to average response rates. "Omics" approaches are used for patient stratification and choice of therapeutic options towards a more precise medicine. These methods, however, do not consider all genetic and non-genetic dynamic interactions that occur upon drug treatment. Therefore, the need to dir

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… Patient-derived xenografts faithfully replicated clinical outcome in a phase II co-clinical trial of arsenic trioxide in relapsed small cell lung cancer. J. Transl. Med. 2016;14:111. doi: 10.1186/s12967-016-0861-5. 92. …

Heterogeneous Contributing Factors in MPM Disease Development and Progression: Biological Advances and Clinical Implications.

Malignant pleural mesothelioma (MPM) tumors are remarkably aggressive and most patients only survive for 5-12 months; irrespective of stage; after primary symptoms appear. Compounding matters is that MPM remains unresponsive to conventional standards of care; including radiation and chemotherapy. Currently; instead of relying on molecular signatures and histological typing; MPM treatment options are guided by clinical stage and patient characteristics because the mechanism of carcinogenesis has not been fully elucidated; although about 80% of cases can be linked to asbestos exposure. Several m

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… Most experimental models report Hh antagonists that target Smo or Gli, such as cyclopamine, vismodegib, GANT61, arsenic trioxide or GLI-I, strongly suppressed MPM cell viability by blocking Gli activation. …

Determining Risk Factors Associated with Cardiovascular Complications in Patients with Acute Leukemia: A Systematic Review.

BackgroundPatients with acute leukemia (AL) are at heightened risk of cardiovascular complications due to both disease-related and treatment-related factors. These complications include heart failure, arrhythmias, myocardial infarction, and thromboembolic events which may significantly impact morbidity and mortality.ObjectiveTo identify the risk factors contributing to cardiovascular complications in patients with acute leukemia.MethodsThis systematic review was conducted according to the PRISMA reporting guideline. Multiple databases including PubMed, Scopus, IEEE Xplore, the Cochrane Library

A novel approach to enhance glioblastoma multiforme treatment efficacy: non-coding RNA targeted therapy and adjuvant approaches.

BackgroundGlioblastoma multiforme (GBM) is a lethal brain tumor. With the current gold standard chemotherapy treatment, temozolomide (TMZ), many patients do not survive beyond one year. While the urgency of researching novel treatments is understandable, the prohibitively high costs and the prolonged duration of research and clinical trials significantly delay the availability of medical advancements to the general public. This highlights the urgent need for adjuvant therapies to enhance treatment effectiveness.Main bodyRecent research has suggested the potential of repurposing FDA-approved dr

Expert consensus on the clinical application of antibody-drug conjugates in the treatment of malignant tumors (2021 edition).

Antibody-drug conjugates (ADCs) are targeted biological agents composed of a cytotoxic drug linked to a monoclonal antibody through a linker. The monoclonal antibody targets tumor cells and transports small-molecule cytotoxic drugs for specific delivery and minimal off-target side effects. It is necessary for clinicians to understand the molecular characteristics and mechanisms of ADCs. Patients' survival mainly depends on the appropriate dose and course of treatment and also on proper management of adverse reactions. This consensus provides a systematic review of commercially available ADCs a

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… The National Comprehensive Cancer Network guidelines recommend GO for the subsequent treatment of high‐risk acute promyelocytic leukemia (APL); or in combination with all‐trans retinoic acid ± arsenic trioxide for relapsed APL; or in combination with standard chemotherapy regimens (cytarabine + daunorubicin …

Journey of TRAIL from Bench to Bedside and its Potential Role in Immuno-Oncology.

Induction of apoptosis in cancer cells has increasingly been the focus of many therapeutic approaches in oncology field. Since its identification as a TNF family member, TRAIL (TNF-related apoptosis-inducing ligand) paved a new path in apoptosis inducing cancer therapies. Its selective ability to activate extrinsic and intrinsic cell death pathways in cancer cells only, independently from p53 mutations responsible for conventional therapeutics resistance, spotted TRAIL as a potent cancer apoptotic agent. Many recombinant preparations of TRAIL and death receptor targeting monoclonal antibodies

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… Wang YR Wen SP Wang FX [Apoptosis of the adriamycin-resistant leukemia cell line induced by the recombinant mutant human TNF-related apoptosis-inducing ligand combined with arsenic trioxide] . Zhongguo shi yan xue ye xue za zhi 2008 ; 16 : 1055 - 9 . 18928594 92. …

Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer.

Macro-autophagy (autophagy) is a highly conserved eukaryotic intracellular process of self-digestion caused by lysosomes on demand, which is upregulated as a survival strategy upon exposure to various stressors, such as metabolic insults, cytotoxic drugs, and alcohol abuse. Paradoxically, autophagy dysfunction also contributes to cancer and aging. It is well known that regulating autophagy by targeting specific regulatory molecules in its machinery can modulate multiple disease processes. Therefore, autophagy represents a significant pharmacological target for drug development and therapeutic

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… | Leukemia | R | NCT01064557 | Gruppo Italiano Malattie VEGFR inhibitor | Adenoid Cystic Carcinoma | 2/R | NCT04433169 | Shanghai Jiao Tong University Tranylcypromine, cytarabine | Acute Myeloid Leukemia | 1/2/R | NCT02717884 | Michael Luebbert - | APL | 2/R | NCT01064570 | Gruppo Italiano Malattie Arsenic … Trioxide, Mylotarg | APL | 2/R | NCT04793919 | Associazione Italiana Ematologia Cytarabine, Arsenic Trioxide | AML | 1/2/R | NCT03031249 | Institute of Hematology and Blood Diseases As an antioxidant agent, N-acetyl cysteine (NAC) effectively abolishes oxidative stress markers, such as intracellular …