arsenic trioxide

P2, N=151, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

All patients received induction therapy with all-trans retinoic acid, arsenic trioxide, or both...Elevated peak WBC, hypoalbuminemia, and lack of prophylactic corticosteroids are independent predictors of DS in APL patients. These findings underscore the importance of early risk stratification and preventive strategies to mitigate DS risk during induction therapy.

The combined impact of TL and ATO amplifies the expression of p65 within the canonical NF-κB signaling pathway, while inhibiting the expression of IkBα, p52, and RelB in the noncanonical pathway. The combination effect of TL and ATO markedly suppresses the proliferation of MDS cells and induces apoptosis collaboratively, which potentially occurs through a mechanism by inhibiting the NF-κB signaling pathway.

The aim of the present study was to monitor the expression of Vim, ENO1, and their citrullinated forms (cit-Vim, cit-ENO1) during the regulation of spontaneous human neutrophil apoptosis (SA) by the antiapoptotic cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) and the proapoptotic anti-cancer drug arsenic trioxide (ATO)...However, Vim, ENO1, cit-Vim, and cit-ENO1 are expressed at the cell surface of apoptotic neutrophils. These data further support the potential participation of neutrophils in autoimmune and inflammatory diseases as they might be an important source of autoantigens when they undergo apoptosis.

Compared to free ATO, the nanomedicine exhibited significantly improved in vivo anti-tumor effects, achieving a 100% 45-day survival rate in mice with favorable biosafety profiles. This study offers novel insights into tumor chemotherapy sensitization and presents a promising strategy for ATO nanoformulation development.

A cigarette compound-formed tumor microenvironment resisted HCC to sorafenib by locking the adaptor protein 14-3-3η in a constitutively active state. This outcome provided a mechanistic rationale and a translational strategy to re-sensitize HCC patients exposed to cigarette to targeted therapy.

Differentiation syndrome (DS) is a serious complication with an unclear pathogenesis that arises following all-trans retinoic acid (ATRA) or arsenic trioxide induction therapy in acute promyelocytic leukemia (APL)...25(OH)D3 also inhibited the ATRA-induced production of cytokines (e.g., IL-8), including IL-1β, TNF-α, and MCP-1, associated with the "cytokine storm." Combined treatment with ATRA plus 25(OH)D3 reduced cellular phospho-p65 and transglutaminase 2 (TG2) levels and increased the level of inhibitor of Rel (IκB), thereby attenuating the cytokine storm. These findings provide a molecular interpretation for clinical DS and IHC observations and may support future exploration of ATRA plus 25(OH)D3 cotreatment as a therapy for APL.

Pro-oxidant therapies aim to overwhelm cellular defenses, with agents like high-dose vitamin C and arsenic trioxide (ATO) showing significant tumor-selective toxicity...Disruption of the GSH system by inhibiting cysteine uptake with sulfasalazine or erastin potently induces ferroptosis, a non-apoptotic cell death driven by lipid peroxidation...Moreover, novel therapeutic strategies, including the expanding field of redox-active metal complexes, such as manganese porphyrins, which strategically leverage the differential redox state of normal versus cancer cells through both pro-oxidant and indirect Nrf2-mediated antioxidative mechanisms (triggered by Keap1 oxidation), with several agents currently in advanced clinical trials, have also been discussed. Essentially, pharmacologically tipping the redox balance beyond the threshold of tolerance offers a rational and powerful approach to eliminate malignant cells, defining a novel frontier for targeted cancer therapy.

Significant differences were observed between the DIC and non-DIC groups in the proportion of patients with initial white blood cells (WBC) ≥5 × 109/L, initial platelets (PLT) ≤26 × 109/L and arsenic trioxide (ATO) use (p < 0.05)...Compared with ATO, RIF is a protective factor during induction therapy. Additionally, FLT3 mutation, PLT ≤26 × 109/L and initial bone marrow blasts ≥90% are independent risk factors for grade 4-5 DIC.

Most patients with APL presented with fever and bleeding. The bcr1 transcript of PML-RARα was the most commonly observed. ATRA and ATO-based treatment was associated with high remission rates, manageable toxicity, and a low relapse rate.

Strategies to mitigate the cardiotoxicity of anticancer therapies and identify patients who may require time-sensitive interventions or long-term follow-up represent promising opportunities to improve the quality and safety of care in the emerging field of cardio-oncology pharmacy.

The introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has dramatically improved outcomes in APL, making it a leading example of successful treatment through differentiation of cancer cells...Zinc also regulates key transcription factors involved in differentiation and proliferation, including RUNX2, KLF4, GFI1, and CREB. In this review, we examine how zinc may impact zinc-finger (ZnF) and non-ZnF transcription factors and differentiation therapy in APL, thereby identifying potential strategies to enhance treatment efficacy and minimize side effects.