P1/2, N=29, Active, not recruiting, University of Colorado, Denver | Trial primary completion date: Apr 2024 --> Dec 2024

P1/2, N=120, Recruiting, National Cancer Institute (NCI) | N=75 --> 120

This study constructed a new cuproptosis-related gene signature that has a good prognostic capacity in assessing the outcome of OC patients. This study enhances our understanding of cuproptosis associated with ovarian cancer aggressiveness, cross-talk with immunocytes, and serves as a novel chemotherapy strategy.

P3, N=705, Recruiting, PharmaMar | Trial completion date: Jun 2025 --> Apr 2026 | Trial primary completion date: Jun 2025 --> Apr 2026

P1/2, N=320, Recruiting, PharmaMar | Trial completion date: Nov 2023 --> Mar 2026 | Trial primary completion date: Nov 2023 --> Mar 2026

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.

P3, N=81, Recruiting, First Affiliated Hospital of Zhejiang University | Not yet recruiting --> Recruiting

P1/2, N=15, Not yet recruiting, Vall d'Hebron Institute of Oncology

ES-Cu can induce cuproptosis in AML cells, which provides a new idea for the treatment of AML.

Acute myeloid leukaemia (AML) is a fatal haematopoietic malignancy and is treated with the conventional combination of cytarabine (Ara-C) and daunorubicin (Dau). HHT synergistically induces apoptosis in combination with Ara-C in vitro and prolongs the survival of xenografts. We provide a new mechanism for AML treatment by regulating the p38 MAPK/H2AX/Mcl-1 axis to improve cytarabine therapy.

Morphological then molecular remissions were achieved with all-trans retinoic acid and Arsenic trioxide...This raises the possibility of an association between such rare disorders. Practical management of APL in the setting of FA-D1 is discussed with an overview of current evidence and knowledge gaps.

P1/2, N=70, Not yet recruiting, University of California, San Francisco | Trial completion date: Oct 2031 --> Jul 2027 | Initiation date: Apr 2024 --> Jul 2024 | Trial primary completion date: Oct 2026 --> Jan 2026

We have previously reported that primary cells from FLT3-ITD mutated AML patients were sensitive to ATO in-vitro compared to other non-M3 AML and molecular/pharmacological inhibition of NF-E2 related factor 2 (NRF2), a master regulator of antioxidant response improved the chemosensitivity to ATO and daunorubicin even in non FLT3-ITD mutated cell lines and primary samples. We examined the effects of molecular/pharmacological suppression of NRF2 on acquired ATO resistance in the FLT3-ITD mutant AML cell line (MV4-11-ATO-R). Digoxin decreased leukemic burden and prolonged survival in MV4-11 ATO-R xenograft mice. We establish that altering NRF2 expression may reverse acquired ATO resistance in FLT3-ITD AML.

P1/2, N=62, Recruiting, Massachusetts General Hospital | Phase classification: P1b/2 --> P1/2

P3, N=81, Not yet recruiting, First Affiliated Hospital of Zhejiang University

As2O3 induces apoptosis and autophagy in liver cancer cells. Autophagy induced by As2O3 may have a proapoptotic effect that helps to reduce the viability of liver cancer cells. This study provides novel insights into the effects of As2O3 against liver cancer. Please cite this article as: Deng ZT, Liang SF, Huang GK, Wang YQ, Tu XY, Zhang YN, Li S, Liu T, Cheng BB. Autophagy plays a pro-apoptotic role in arsenic trioxide-induced cell death of liver cancer. J Integr Med. 2024; Epub ahead of print.

P1, N=15, Not yet recruiting, Neonc Technologies, Inc.

P=N/A, N=300, Recruiting, Jazz Pharmaceuticals | Active, not recruiting --> Recruiting | Trial completion date: Jan 2026 --> Jun 2030 | Trial primary completion date: Oct 2025 --> Jun 2030

Targeting MILIP inhibited TNBC growth and cooperated with the clinically available protein synthesis inhibitor omacetaxine mepesuccinate in vivo. Collectively, these results identify MILIP as an RNA translation elongation factor that promotes protein production in TNBC cells and reveal the therapeutic potential of targeting MILIP, alone and in combination with other types of protein synthesis inhibitors, for TNBC treatment. LncRNA MILIP plays a key role in supporting protein production in TNBC by forming complexes with tRNAs and eEF1α1, which confers sensitivity to combined MILIP targeting and protein synthesis inhibitors.

Homoharringtonine, a Food And Drug Administration-approved translation elongation inhibitor, impedes CRPC progression in preclinical models and patients with CRPC. We construct an SCLPC-specific signature capable of stratifying patients for drug selectivity. Our studies reveal the existence of SCLPC in admixed PCa pathology, which may mediate tumor relapse, and establish SP1 and translation elongation as actionable therapeutic targets for CRPC.

P2, N=109, Active, not recruiting, Promontory Therapeutics Inc. | Recruiting --> Active, not recruiting | N=180 --> 109

P2, N=35, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

P2, N=25, Recruiting, Mridula George, MD | Trial primary completion date: Jan 2024 --> Jun 2024

P1, N=9, Terminated, H. Lee Moffitt Cancer Center and Research Institute | Phase classification: P1/2 --> P1

Despite these promising in vitro effects, omacetaxine's efficacy in an orthotopic DIPG model was limited due to inadequate penetration across the blood-brain barrier. As such, further research and advancements are crucial to improve the drug's brain penetration, thus enhancing its overall therapeutic potential.

More so, there seems to be a lower incidence rate of secondary neoplasms compared to standard chemotherapy. However, further research is required to assess how the ATRA plus ATO regimen affects the emergence of additional comorbidities.

In a comprehensive the drug susceptibility analysis, we found that patients with high expression of CDC45 had high sensitivity to various chemotherapeutic agents, among which 5-fluorouracil, docetaxel, cisplatin, and elesclomol were most evident. Enrichment analysis revealed that CDC45 and its associated genes may play crucial roles in muscle biofunction, whereas GSEA demonstrated significant enrichment of gene sets pertaining to G protein-coupled receptor ligand binding and G alpha (i) signaling events. Our study elucidates that upregulation of CDC45 is intricately associated with immune cell infiltration and holds promising potential as a favorable prognostic marker and a novel diagnostic biomarker for GC.

P=N/A, N=34, Recruiting, Huai'an First People's Hospital

P1, N=1, Terminated, Bellicum Pharmaceuticals | Active, not recruiting --> Terminated; due to lack of enrollment and changes to the sponsor development portfolio

The synergy of AZA+HHT on apoptosis was induced by activating c-MYC/DDIT3/PUMA-mediated ISR signaling. The combination of AZA and HHT exerts synergistic anti-AML effects by inhibiting cellular proliferation and promoting apoptosis through activation of the ISR signaling pathway via the c-MYC/DDIT3/PUMA axis.

P1/2, N=29, Active, not recruiting, University of Colorado, Denver | Recruiting --> Active, not recruiting | N=45 --> 29

VC with arsenic trioxide (ATO) is a promising drug combination that might lead to the development of effective cancer therapeutics...Thus, our study indicates that the two enantiomers of VC have a similar potency in the induction of oxidative stress in cancer cells, but D-VC has a distinctive lower toxicity in mice compared to L-VC. While the mechanism of a distinctive toxicity between D-VC and L-VC is yet to be defined, our finding marks D-VC as a more preferable option compared to its natural enantiomer L-VC in clinical settings.

Finally, ZC3H13 overexpression alleviated the inhibitory effects of ATO on LASCs tumorigenicity. Taken together, ATO treatment substantially impaired the stemness of LUAD stem cells by promoting the ferroptosis program, which was mediated by its ZC3H13 gene expression inhibition to suppress m6A medication.

P=N/A, N=300, Active, not recruiting, Jazz Pharmaceuticals | Recruiting --> Active, not recruiting

In the SAINT phase 2 study using ipi, nivo and trabectedin as first line therapy for advanced soft tissue sarcomas (STS; n=79), there were 6 complete responses, 14 partial responses, 49 stable disease, 25.3% best response rate, 87.3% disease control rate; median PFS, 6.7 months, median OS, 24.6 months (Gordon et al, Cancers vol. Eligible patients are 18 years of age or older, previously treated in phase 1 and previously untreated in phase 2 with confirmed diagnosis of advanced STS, adequate hematologic and organ function, and no history of autoimmune disorder. To date, 6 patients in phase 1 have been dosed.

The drug combination of GZ17-6.02 and bortezomib activated ATM, the AMPK and PERK and inactivated ULK1, mTORC1, eIF2α, NFκB and the Hippo pathway. HDAC knock down also enhanced ATG13 phosphorylation, increased BAK levels and reduced those of BCL-XL. Collectively, our present studies support performing additional in vivo studies with multiple myeloma cells.

Metformin can synergize with arsenic trioxide to kill KG1a cells, and its mechanism of action may be related to inducing apoptosis and enhancing autophagy.

P2, N=47, Completed, Jazz Pharmaceuticals | Active, not recruiting --> Completed

P2, N=30, Recruiting, First Affiliated Hospital of Zhejiang University | Trial completion date: Aug 2024 --> Jun 2025 | Initiation date: Oct 2022 --> Jun 2023 | Trial primary completion date: Dec 2023 --> Dec 2024

No differences in terms of toxicity were found between LRB with and without BOS. In summary, the magnitude of the observed changes precludes a clinically relevant effect of BOS co-administration on LRB exposure and its safety profile.

The treatment of acute promyelocytic leukemia (APL) has evolved with the introduction of all-trans retinoic acid (ATRA) and subsequent arsenic trioxide (ATO), particularly in standard-risk APL with an initial white blood cell count (WBC) < 10,000/μL, where a high cure rate can now be achieved...However, in the ATRA + ATO era, the significance of these risk factors is changing. This article provides a comprehensive review of APL risk factors, taking into account the treatment approach, and explores the challenges associated with APL treatments.

In our study, we demonstrated that elesclomol, as a carrier of copper ions, caused an upregulation of protein phosphatase 1 regulatory subunit 15 A (PPP1R15A), which plays a role in regulating substrate selectivity of protein phosphatase 1 during cuproptosis. Mechanistically, we investigated that PPP1R15A activated translation initiation by dephosphorylating eukaryotic translation initiation factor 2 subunit alpha at the S51 residue through protein phosphatase 1 and phosphorylating eukaryotic translation initiation factor 4E binding protein 1 at the T70 residue. In addition, PPP1R15A reduced H3K4 methylation by altering the phosphorylation of histone methyltransferases, which led to the silencing of MYC and G2M phase arrest.