arsenic trioxide

Although arsenic trioxide (ATO) can restore transcriptional activity of structural p53 mutants, its clinical application is limited by subtype selectivity and systemic toxicity...Upon tumor-specific release, allicin-mediated redox activation converts As5+ to cytotoxic As3+, enabling selective p53 reactivation, concurrent ATR inhibition, and H2S-amplified apoptosis. AsAcP@LP exhibits synergistic antitumor efficacy with favorable tolerability, providing a rational nanotherapeutic strategy for p53-mutant cancers.

(3) Clinical evidence confirms that ATRA combined with arsenic trioxide or epigenetic modulators achieves high remission rates in APL and selected AML subtypes...(4) ATRA-based combination therapies represent a promising strategy to extend differentiation therapy beyond APL. This review, authored solely by the investigator, highlights molecular targets and potential enhancers warranting further clinical evaluation in AML.

The mechanisms involve suppressing ROS generation, maintaining mitochondrial membrane stability, enhancing cell viability, migration, and proliferation, as well as inhibiting Jnk and p38 mitogen-activated protein kinase (p38 MAPK) signaling pathways. The findings highlight potential molecular targets and novel strategies for the clinical prevention and treatment of ATO-related toxicity .

ATO combined with MET promotes apoptosis by up-regulating LKB1/AMPK and down-regulating PI3K/Akt signaling pathway to regulate the autophagy of leukemia cells.

We demonstrate that the E3 ligase UBE2O catalyzes dual-site monoubiquitination of NLRP6: at K680-687 to drive oligomerization via a conformational change, and at K115/130 within the nuclear localization signal to enforce cytoplasmic sequestration through steric hindrance. Furthermore, the UBE2O inhibitor arsenic trioxide suppresses NLRP6-dependent interleukin (IL)-18 secretion in acute promyelocytic leukemia (APL) patients. Thus, UBE2O-mediated dual-site monoubiquitination emerges as a central mechanism licensing NLRP6 inflammasome activation, revealing a new target for modulating intestinal immunity.

Furthermore, the article explores the importance of the immune system in acute promyelocytic leukemia treatment response and the impact of all-trans retinoic acid/arsenic trioxide therapy on the proteome and metabolome. By synthesizing existing research findings, this review aims to discuss how proteomic and metabolomic data elucidate the pathological mechanisms and therapeutic targets of acute promyelocytic leukemia, providing a theoretical basis for future precision medicine and translational research.

Despite the high efficacy of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) in treating acute promyelocytic leukemia (APL), approximately 10-20% of patients develop drug resistance due to mutations in PML-RARα and other factors...Consistent with PML-RARα degradation, ML364 treatment significantly induces apoptosis in APL cell lines and primary leukemia cells. In conclusion, this study identifies USP2 as a novel deubiquitinating enzyme for PML-RARα and highlights USP2 inhibition as a potential therapeutic strategy for APL with PML-RARα mutations.

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia characterized by the promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA) fusion gene and exceptional responsiveness to differentiation therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (Arsenic Trioxide)...Anthracycline-based chemotherapy was subsequently administered, followed by azacitidine combined with venetoclax in the subsequent course of treatment...A literature review suggests that FIP1L1-RARA-positive APL represents a biologically and clinically distinct entity with highly variable treatment responses and poor prognosis. Early molecular diagnosis and prompt implementation of conventional chemotherapy or targeted therapies such as venetoclax may be essential to improving outcomes in this rare APL subtype.

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.