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DRUG:

arsenic trioxide

i
Other names: NSC-706363, As2O3
Company:
Generic mfg.
Drug class:
Apoptosis stimulant
15d
Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia (clinicaltrials.gov)
P3, N=158, Active, not recruiting, Children's Oncology Group | Trial completion date: Sep 2024 --> Sep 2025
Trial completion date
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FLT3 (Fms-related tyrosine kinase 3) • RARA (Retinoic Acid Receptor Alpha) • PML (Promyelocytic Leukemia)
|
FLT3 mutation • FLT3 wild-type
|
cytarabine • idarubicin hydrochloride • mitoxantrone • Vesanoid (tretinoin) • arsenic trioxide • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate)
16d
Low-dose arsenic trioxide inhibits pancreatic stellate cell activation via LOXL3 expression to enhance immunotherapy in pancreatic cancer. (PubMed, Br J Cancer)
Our research reveals that low-dose ATO, by regulating LOXL3, remodels the ECM and enhances CD8+T cell infiltration, thus sensitizing the efficacy of immunotherapy, which provides a novel strategy for comprehensive treatment to PC.
Journal • PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8)
|
arsenic trioxide
21d
Oral Arsenic (ATO) in Low-risk Myelodysplastic Syndromes (MDS) (clinicaltrials.gov)
P1, N=24, Not yet recruiting, Groupe Francophone des Myelodysplasies
New P1 trial
|
arsenic trioxide • Reblozyl (luspatercept-aamt)
1m
Ischemic stroke as a presenting feature of promyelocytic blast phase in chronic myeloid leukemia - an uncommon presentation: a case report and literature review in the post imatinib era. (PubMed, Ann Hematol)
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm (MPN characterized by reciprocal translocation in the ABL1 and BCR region of chromosomes 9 and 22 respectively. We report a case of CML who presented to us with acute ischemic stroke and subsequently was diagnosed as CML transformed to the promyelocytic blast phase. She was successfully treated with dasatinib along with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO).
Review • Journal
|
ABL1 (ABL proto-oncogene 1)
|
dasatinib • imatinib • arsenic trioxide
2ms
The anti-inflammatory effect of arsenic trioxide effectively mitigates the pathogenic process in local chickens with avian leukosis. (PubMed, Poult Sci)
In conclusion, the anti-inflammatory effect of ATO can effectively alleviate the ALV-J pathogenic process. ALV-J serves as a model virus for antiviral tumor research, while ATO provides references for the treatment of such tumors.
Journal • IO biomarker
|
TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • TLR4 (Toll Like Receptor 4) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • IL1B (Interleukin 1, beta)
|
BCL2 expression • TP53 expression
|
arsenic trioxide
2ms
Effects of imidazole derivatives on cellular proliferation and apoptosis in myeloid leukemia. (PubMed, BMC Cancer)
Imidazole derivatives significantly reduce proliferation of NB4 and K562 cells by inducing apoptosis, down regulating of AXL-RTK and Wnt/β-catenin target genes.
Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog)
|
imatinib • arsenic trioxide
2ms
Short-term results of a multicenter study based on a modified N7 induction regimen combined with arsenic trioxide in the treatment of children with high-risk neuroblastoma (PubMed, Zhonghua Er Ke Za Zhi)
There were no chemotherapy-related deaths. ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
arsenic trioxide
2ms
Case report: Successful therapy with azacitidine for acute myeloid leukemia with NUP98::RARG resembling acute promyelocytic leukemia. (PubMed, Front Oncol)
AML with RARG rearrangement is insensitive to all-trans retinoic acid (ATRA) and arsenic trioxide. The patient received azacitidine therapy after failing ATRA and standard 3 + 7 therapy (idarubicin and cytarabine) and achieved complete remission. Conclusively, this acute myeloid leukemia subtype may benefit from azacitidine.
Journal
|
NUP98 (Nucleoporin 98 And 96 Precursor 2) • RARG (Retinoic Acid Receptor Gamma)
|
cytarabine • azacitidine • idarubicin hydrochloride • arsenic trioxide
2ms
Phytochemical profiling and anticancer potential of gardenia latifolia extracts against arsenic trioxide induced liver fibrosis in rat model. (PubMed, Front Pharmacol)
Group II was taken as positive control, Group III and IV were treated with ethanol and n-hexane extract of G. latifolia, respectively, and Group V was treated with cisplatin 3.0 mg/kg/day. In conclusion, the effective therapeutic potential of G. latifolia extracts targeted oxidative stress, increasing antioxidant activities and inhibiting inflammation and liver complications at early stages. Further research on the molecular level may further explore the anticancer potential of this plant against various types of cancers.
Preclinical • Journal
|
IL6 (Interleukin 6) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
|
cisplatin • arsenic trioxide
2ms
Successfully treatment of PLZF-RARα positive acute promyelocytic leukemia by Venetoclax combining with decitabine: a case report and literature review. (PubMed, Hematology)
The patient did not respond to all-trans retinoic acid (ATRA), idarubicin, and arsenic trioxide (As2O3) combined induction chemotherapy. Then, the patient was treated with Venetoclax combining with decitabine as the salvage therapy and achieved morphological remission and PLZF/RARα gene negative. Venetoclax combining with decitabine can be used as an effective therapy in the PLZF-RARα positive APL.
Review • Journal
|
RARA (Retinoic Acid Receptor Alpha) • PML (Promyelocytic Leukemia) • RARG (Retinoic Acid Receptor Gamma)
|
Venclexta (venetoclax) • decitabine • idarubicin hydrochloride • arsenic trioxide
2ms
Leucocytosis during induction therapy with all-trans-retinoic acid and arsenic trioxide in acute promyelocytic leukaemia predicts differentiation syndrome and treatment-related complications. (PubMed, Br J Haematol)
All cases were successfully managed with hydroxyurea...In conclusion, APL patients undergoing ATRA-ATO therapy with lower fibrinogen levels and platelet counts at diagnosis and with a massive bone marrow blast infiltrate should be carefully monitored for the development of leucocytosis during induction. DS and other treatment-related complications seem to occur almost exclusively in patients developing leucocytosis, who should necessarily receive DS prophylaxis and more intensive monitoring and supportive therapy to prevent treatment complications.
Journal
|
KIT (KIT proto-oncogene, receptor tyrosine kinase)
|
KIT expression
|
Vesanoid (tretinoin) • arsenic trioxide • hydroxyurea
3ms
Palmitoyltransferase ZDHHC3 is essential for the oncogenic activity of PML/RARα in acute promyelocytic leukemia. (PubMed, Acta Pharmacol Sin)
The standard clinical therapies all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), which induce PML/RARα proteolysis, have dramatically improved the prognosis of APL patients...Consistently, the depletion or inhibition of ZDHHC3 could significantly arrest the malignant progression of APL, particularly drug-resistant APL, whereas ZDHHC3 overexpression appeared to have a promoting effect on the malignant progression of APL. Thus, our study not only reveals palmitoylation as a novel regulatory mechanism that modulates PML/RARα oncogenic activity but also identifies ZDHHC3 as a potential therapeutic target for APL, including drug-resistant APL.
Journal
|
RARA (Retinoic Acid Receptor Alpha)
|
arsenic trioxide
3ms
Combination of arsenic trioxide and apatinib synergistically inhibits small cell lung cancer by down-regulating VEGFR2/mTOR and Akt/c-Myc signaling pathway via GRB10. (PubMed, Hereditas)
Synergistically, ATO and APA have a more significant impact on inhibiting cell proliferation than each drug independently. ATO and APA may be mediating its action through the stabilization of GRB10 thus acting as a tumor suppressor. We thus, preliminarily report the impact of GRB10 stability as a target for SCLC treatment.
Journal
|
KDR (Kinase insert domain receptor) • CASP3 (Caspase 3)
|
AiTan (rivoceranib) • arsenic trioxide
3ms
Distinct In Vitro Differentiation Protocols Differentially Affect Cytotoxicity Induced by Heavy Metals in Human Neuroblastoma SH-SY5Y Cells. (PubMed, Biol Trace Elem Res)
Therefore, we investigated the effects of mercuric chloride (HgCl2), cadmium chloride (CdCl2), arsenic trioxide (As2O3), and methylmercury (MeHg) on SH-SY5Y cells differentiated in the presence of insulin-like growth factor-I (IGF-I) or all-trans retinoic acid (ATRA)...Changes in the cytotoxic effects of heavy metals were observed even after 1 day of ATRA exposure in SH-SY5Y cells. Our results demonstrate that the differentiation of SH-SY5Y cells by IGF-I and ATRA induces different cellular characteristics, resulting in diverse changes in sensitivity to heavy metals, which depend not only on the differentiation agents and treatment time but also on the heavy metal species and concentration.
Preclinical • Journal
|
IGF1 (Insulin-like growth factor 1)
|
arsenic trioxide
3ms
Enhanced depletion of MLL-fusion proteins in acute leukemia: potential for improved therapeutic outcomes. (PubMed, Exp Hematol Oncol)
Inspired by the paradigm of depleting the PML-RARA fusion protein in acute promyelocytic leukemia using all-trans retinoic acid and arsenic trioxide, we conducted a screen to identify FDA-approved drugs capable of depleting MLL-fusion protein expression in leukemia cells. Previously, we reported potent anti-leukemia effects of disulfiram (DSF), identified through this screen. In the present study, we demonstrate that another hit compound, niclosamide (NSM), is also able to deplete MLL-fusion proteins derived from a range of different MLL-fusion genes in both acute myeloid (AML) and acute lymphoid (ALL) leukemias...In contrast, DSF/NSM drug combination had little impact on normal hematopoietic progenitor cell differentiation. This study demonstrates that two FDA-approved drugs with excellent safety profiles can be combined to increase the efficacy of MLL-fusion protein depletion and elimination of MLL-rearranged leukaemia.
Journal
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KMT2A (Lysine Methyltransferase 2A) • PML (Promyelocytic Leukemia)
|
arsenic trioxide • niclosamide
3ms
TRIM44 enhances autophagy via SQSTM1 oligomerization in response to oxidative stress. (PubMed, Sci Rep)
In this study, we demonstrate that TRIM44 significantly enhances autophagy in response to oxidative stress, reducing cytotoxicity in cancer cells treated with arsenic trioxide...This phosphorylation event activates NFE2L2, a key transcription factor in the oxidative stress response, highlighting the importance of TRIM44 in modulating SQSTM1-mediated autophagy. Our findings support that TRIM44 plays pivotal roles in regulating autophagic sensitivity to oxidative stress, with implications for cancer, aging, aging-associated diseases, and neurodegenerative disorders.
Journal
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SQSTM1 (Sequestosome 1) • TRIM4 (Tripartite Motif Containing 4)
|
arsenic trioxide
3ms
Arsenic trioxide and p97 inhibitor synergize against acute myeloid leukemia by targeting nascent polypeptides and activating the ZAKα-JNK pathway. (PubMed, Cancer Gene Ther)
Importantly, our data revealed that inhibiting p97 enhanced the effectiveness of ATO in killing AML cells. These explorations paved the way for identifying optimal synthetic lethal drugs to enhance ATO treatment on non-APL AML.
Journal
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RARA (Retinoic Acid Receptor Alpha) • PML (Promyelocytic Leukemia) • ATF4 (Activating Transcription Factor 4)
|
arsenic trioxide
4ms
Synergistic rescue of temperature-sensitive p53 mutants by hypothermia and arsenic trioxide. (PubMed, Mol Carcinog)
The results suggest that mild TS p53 mutants are uniquely responsive to functional rescue by ATO due to small thermostability deficits and inherent potential to regain active conformation. Combining mild hypothermia and ATO may provide an effective and safe procedure for targeting tumors with p53 TS mutations.
Journal
|
TP53 (Tumor protein P53)
|
arsenic trioxide
4ms
Outcomes of Acute Promyelocytic Leukaemia in Paediatric Patients: Insights from a Low-Middle-Income Country. (PubMed, J Coll Physicians Surg Pak)
Neutropenic fever and bleeding were the primary causes of mortality in paediatric APL induction. Treatment delay was a key prognostic factor. ATO-based therapy offered safer, improved DFS, and OS suitable for primary healthcare settings.
Journal
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RARA (Retinoic Acid Receptor Alpha) • PML (Promyelocytic Leukemia)
|
arsenic trioxide
4ms
Arsenic Trioxide With Cyclophosphamide in Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov)
P1, N=5, Terminated, University of Colorado, Denver | Completed --> Terminated; Low enrollment, University Scientific Review Committee required study closure.
Trial termination
|
cyclophosphamide • arsenic trioxide
4ms
Arsenic trioxide regulates the glycolytic pathway to treat acute promyelocytic leukemia by inhibiting RPL22L1. (PubMed, Leuk Res)
ATO regulates the blycolytic pathway in APL by inhibiting RPL22L1 expression, and this may contribute to its therapeutic effects.
Journal
|
RPL22L1 (Ribosomal Protein L22 Like 1)
|
arsenic trioxide
4ms
Diosgenin alleviates arsenic trioxide induced cardiac fibrosis by inhibiting endothelial mesenchymal transition. (PubMed, Phytomedicine)
In this study, we clarified the protective effect of DIO on ATO-induced myocardial fibrosis against EndMT via the GR/IL-6 axis for the first time and provided a potential therapeutic agent for preventing heart damage caused by ATO.
Journal
|
IL6 (Interleukin 6) • CD31 (Platelet and endothelial cell adhesion molecule 1) • PECAM1 (Platelet And Endothelial Cell Adhesion Molecule 1)
|
arsenic trioxide
4ms
Disruption of cyclin D1 degradation leads to the development of mantle cell lymphoma. (PubMed, Acta Pharm Sin B)
We showed that arsenic trioxide (ATO) enhances cyclin D1 SUMOylation-mediated degradation through inhibition of cyclin D1 deSUMOylation enzymes, leading to MCL cell apoptosis. Treatment of severe combined immunodeficiency (SCID) mice grafted with MCL cells with ATO resulted in a significant reduction in tumor growth. In this study, we provide novel insights into the mechanisms of MCL tumor development and cyclin D1 regulation and discover a new strategy for MCL treatment.
Journal
|
CCND1 (Cyclin D1)
|
arsenic trioxide
4ms
Function of PML-RARA in Acute Promyelocytic Leukemia. (PubMed, Adv Exp Med Biol)
PML-RARA mainly acts as a modulator of the expression of specific target genes: genes whose regulatory elements recruit PML-RARA are not uniformly repressed but also may be upregulated or remain unchanged. RA and arsenic trioxide directly target PML-RARA-mediated transcriptional deregulation and protein stability, removing the differentiation block at promyelocytic stage and inducing clinical remission of APL patients.
Review • Journal
|
PML (Promyelocytic Leukemia)
|
arsenic trioxide
4ms
Green-synthesized copper oxide nanoparticles induce apoptosis and up-regulate HOTAIR and HOTTIP in pancreatic cancer cells. (PubMed, Nanomedicine (Lond))
SLCu2O NPs demonstrated anti-cancer properties against PANC-1 cells comparable to Arsenic trioxide, and the expression of lncRNAs increased upon treatment with them. SLCu2O NPs demonstrate anti-cancer properties against PANC-1 cells; however, using gene silencing strategies along with SLCu2O NPs is suggested.
Journal
|
HOTAIR (HOX Transcript Antisense RNA) • HOTTIP (HOXA Distal Transcript Antisense RNA)
|
arsenic trioxide
5ms
How I Treat: Differentiation Therapy in Acute Myeloid Leukemia. (PubMed, Blood)
All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are classic examples of differentiating agents for treatment of acute promyelocytic leukemia (APL); newer therapies functioning through differentiation include isocitrate dehydrogenase (IDH) 1 and 2 inhibitors, FMS-like tyrosine kinase 3 (FLT3) inhibitors, and menin inhibitors...DS in patients with newly diagnosed APL is generally straightforward to identify, however DS in patients with multiply relapsed AML can be more challenging to diagnose, due to non-specific signs and symptoms which can be mistakenly attributed to infectious etiologies or the underlying refractory leukemia itself. Prompt consideration of DS, rapid initiation of systemic corticosteroids, and early cytoreduction in the setting of concomitant hyperleukocytosis, are essential for optimal management.
Journal
|
FLT3 (Fms-related tyrosine kinase 3)
|
arsenic trioxide
5ms
Molecular Interactions of Selective Agonists and Antagonists with the Retinoic Acid Receptor γ. (PubMed, Int J Mol Sci)
ATRA with arsenic trioxide has provided a cure for the once highly fatal leukemia...At the same time, it is important to retain isotype specificity and activity. Examination of the molecular interactions between RARγ agonists and the ligand binding domain of RARγ has revealed aspects to ligand binding that are crucial to RARγ selectivity and compound activity and key to designing newer compounds.
Review • Journal
|
RARA (Retinoic Acid Receptor Alpha) • PML (Promyelocytic Leukemia)
|
arsenic trioxide
5ms
Acute Promyelocytic Leukemia With Long and Short Isoforms of PML::RARA Fusion Transcripts Complicated by Abdominal Distension and Acute Edematous Pancreatitis During Induction Treatment: A Case Report. (PubMed, Cureus)
The introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has transformed the outcome of acute promyelocytic leukemia (APL) from a uniformly fatal disease to one of the most curable human malignancies in recent decades...Therefore, these drugs were adjusted to the maximum tolerated dose based on the experience with the initial induction treatment, and the patient achieved CR after four weeks of reinduction treatment. We report that this case may provide some clinical information for the diagnosis and treatment of similar patients with APL.
Journal
|
FLT3 (Fms-related tyrosine kinase 3)
|
arsenic trioxide
5ms
Nano-fenretinide demonstrates remarkable activity in acute promyeloid leukemia cells. (PubMed, Sci Rep)
Current therapy, based on ATRA in combination with arsenic trioxide, with or without chemotherapy, provides high rates of event-free survival and overall survival. Nano-fenretinide was effective, albeit at slightly higher concentrations, also in doxorubicin-resistant HL60 cells, while a comparison with TK6 lymphoblasts indicated a lack of toxicity on normal cells. The results indicate that nano-fenretinide can be considered an alternative therapy to ATRA in acute promyelocytic leukemia when decreased efficacy, resistance or recurrence of disease emerge after protracted treatments with ATRA.
Journal
|
RARA (Retinoic Acid Receptor Alpha)
|
doxorubicin hydrochloride • arsenic trioxide
5ms
Negative expression of CD117 predicted inferior OS and PFS in acute promyelocytic leukemia. (PubMed, Int J Lab Hematol)
To sum up, CD117- is associated with greater risk of ED and has the statistical power to predict inferior OS and PFS, this marker may be considered to build prognostic scores for risk-adapted therapeutic strategies in APL management.
Journal
|
KIT (KIT proto-oncogene, receptor tyrosine kinase)
|
arsenic trioxide
5ms
Targeting mutant p53 with arsenic trioxide: A preclinical study focusing on triple negative breast cancer. (PubMed, Transl Oncol)
Direct evidence of mutant p53 reactivation was the induction of multiple wild-type p53 canonical target genes such as CDKN1A, SLC7A11, BBC3, PMAIP1, SESN2, SRXN1 and TXNRD1. Our findings support the activation of mutant p53 by ATO and, furthermore, the possible repurposing of ATO to treat TP53-mutated TNBC.
Preclinical • Journal
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TP53 (Tumor protein P53) • PMAIP1 (Phorbol-12-Myristate-13-Acetate-Induced Protein 1) • SLC7A11 (Solute Carrier Family 7 Member 11) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • SESN2 (Sestrin 2) • BBC3 (BCL2 Binding Component 3)
|
eprenetapopt (APR-246) • arsenic trioxide
5ms
Structural basis of p53 inactivation by cavity-creating cancer mutations and its implications for the development of mutant p53 reactivators. (PubMed, Cell Death Dis)
Differential stabilization of the mutants upon treatment with the anticancer agent arsenic trioxide and stibogluconate revealed an interesting proximity effect...Intriguingly, our structural studies suggest a pronounced plasticity of the mutation-induced pocket in the frequently occurring Y163C mutant, which may be exploited for the development of small-molecule stabilizers. We point out general principles for reactivating thermolabile cancer mutants and highlight special cases where mutant-specific drugs are needed for the pharmacological rescue of p53 function in tumors.
Journal
|
TP53 (Tumor protein P53)
|
arsenic trioxide
5ms
New trial
|
Venclexta (venetoclax) • arsenic trioxide
6ms
Arsenic Trioxide Suppresses Angiogenesis in Non-small Cell Lung Cancer via the Nrf2-IL-33 Signaling Pathway. (PubMed, Anticancer Agents Med Chem)
Nrf2-IL-33 signaling is usually activated in NSCLC and positively correlates with tumor angiogenesis. ATO effectively disrupts the activation of the Nrf2-IL-33 pathway in NSCLC and thus inhibits angiogenesis, suggesting its potential as an anti-angiogenic agent for use in the treatment of NSCLC.
Journal
|
NFE2L2 (Nuclear Factor, Erythroid 2 Like 2) • CD31 (Platelet and endothelial cell adhesion molecule 1) • PECAM1 (Platelet And Endothelial Cell Adhesion Molecule 1) • IL33 (Interleukin 33)
|
arsenic trioxide
6ms
Clinically used drug arsenic trioxide targets XIAP and overcomes apoptosis resistance in an organoid-based preclinical cancer model. (PubMed, Chem Sci)
Drug resistance in tumor cells remains a persistent clinical challenge in the pursuit of effective anticancer therapy. Importantly, we further demonstrate that arsenic sensitized a variety of apoptosis-resistant cancer cells, including patient-derived colon cancer organoids, to the chemotherapy drug using cisplatin as a showcase. These findings suggest that targeting XIAP with ATO offers an attractive strategy for combating apoptosis-resistant cancers in clinical practice.
Preclinical • Journal
|
XIAP (X-Linked Inhibitor Of Apoptosis)
|
cisplatin • arsenic trioxide
6ms
Comparative analysis of immunological changes following realgar and arsenic trioxide treatments in a murine model of myelodysplastic syndrome. (PubMed, Immunopharmacol Immunotoxicol)
In addition, there were interactions between immune cells in the peripheral blood, spleen, and liver to regulate the immune balance of the body and activate immunity via T-cell activation. In summary, oral and intravenous arsenic agents are beneficial in improving peripheral hemogram and immunity in mice.
Clinical • Preclinical • Journal
|
NUP98 (Nucleoporin 98 And 96 Precursor 2)
|
arsenic trioxide
6ms
Combination Effect of Deferoxamine and Arsenic Trioxide on Viability and Vitality of APL Like Cell Line. (PubMed, Ethiop J Health Sci)
In addition, this combination causes an increase in apoptosis, up-regulation of Caspase-3, and down-regulation of hTERT genes in cells. Combined ATO/ DFO treatment cooperatively decreased the mRNA levels of the hTERT and increased the mRNA levels of Caspase-3 in a time-dependent manner compared to DFO alone.
Preclinical • Journal
|
TERT (Telomerase Reverse Transcriptase) • CASP3 (Caspase 3)
|
arsenic trioxide
6ms
N-acetylcysteine alleviates arsenic trioxide-induced reductions in hepatic catalase gene expression both in vitro and in vivo. (PubMed, Leg Med (Tokyo))
Additionally, NAC played a role in alleviating ATO-induced hepatotoxicity, potentially by mitigating the transcriptional downregulation of the CAT gene. Altogether, these results indicate that ATO exerts toxicity by inhibiting the antioxidant defense mechanism, which may be useful for forensic diagnosis of arsenic poisoning and clinical treatment of mitigating ATO-induced hepatotoxicity.
Preclinical • Journal
|
PPARG (Peroxisome Proliferator Activated Receptor Gamma) • CAT (Catalase)
|
arsenic trioxide
6ms
Orphan nuclear receptors-induced ALT-associated PML bodies are targets for ALT inhibition. (PubMed, Nucleic Acids Res)
Moreover, PML depletion by gene knockout or arsenic trioxide treatment inhibited ALT induction in fibroblasts and ALT cancer cells, suggesting that APB formation underlies the orphan NR-induced ALT activation. Importantly, arsenic trioxide administration abolished APB formation and features of ALT activity in ALT cancer cell line-derived mouse xenografts, suggesting its potential for further therapeutic development to treat ALT cancers.
Journal
|
ATRX (ATRX Chromatin Remodeler) • DAXX (Death-domain associated protein)
|
arsenic trioxide
6ms
The carcinogenic capacity of arsenic in normal epithelial breast cells and double-positive breast cancer cells. (PubMed, Med Pharm Rep)
In our current research, we aimed to simulate the effects of chronic low-level arsenic exposure on breast cells by intoxicating MCF-10A and MCF-7 cells with 1 μM Arsenic trioxide (As2O3) for 3 weeks (3w) and 6 weeks (6w), respectively...Furthermore, MCF-7 cells exhibited unique mutations in the KIT Proto-Oncogene (KIT) (c.1594G>A) and TP53 (c.215C>G). In summary, our study reveals that a 6-weeks exposure to arsenic has a limited carcinogenic effect in normal breast cells and a dual role in breast cancer cells.
Journal • Tumor mutational burden
|
HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • FLT3 (Fms-related tyrosine kinase 3) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • KDR (Kinase insert domain receptor) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • CSF1R (Colony stimulating factor 1 receptor) • SMARCD3 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily D, Member 3)
|
TP53 mutation • HER-2 mutation • KIT mutation
|
arsenic trioxide
6ms
SOHO State of the Art Updates and Next Questions: Pre-emptive Therapy at Molecular Measurable Residual Disease Failure in Acute Myeloid Leukemia. (PubMed, Clin Lymphoma Myeloma Leuk)
In acute promyelocytic leukemia, arsenic trioxide-based regimen for MRD failure following frontline treatment with all-trans-retinoic acid plus chemotherapy represents standard of care, while hypomethylating agents (eg, azacitidine), salvage chemotherapy (eg, FLAG-IDA) and venetoclax-based regimens are effective in NPM1-mutated AML. Enrollment into clinical trials with genomic-guided assignment of pre-emptive therapy at MRD failure should be prioritized. Finally, with the emergence of novel agents (eg, menin inhibitors) and approaches (eg, adoptive cellular and immunological therapy), an exciting future lies ahead where a broad array of highly active pre-emptive therapeutic options will likely be clinically applicable to a wide range of AML subsets.
Review • Journal • IO biomarker
|
FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)
|
FLT3 mutation • NPM1 mutation
|
Venclexta (venetoclax) • azacitidine • arsenic trioxide
7ms
Arsenic trioxide augments immunogenic cell death and induces cGAS-STING-IFN pathway activation in hepatocellular carcinoma. (PubMed, Cell Death Dis)
In summary, our data indicate that heterogeneous ATO responses exist in HCC tumors, and ATO treatment significantly induces immunogenic cell death (ICD) and activates the tumor-derived mtDNA-STING-IFN axis. These findings may offer a new perspective on the clinical treatment of HCC and warrant further study.
Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • STING (stimulator of interferon response cGAMP interactor 1)
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PD-L1 expression
|
arsenic trioxide